The APOL1 NM_003661.4:c.1164_1169del (NP_003652.2:p.(Asn388_Tyr389del)) in-frame deletion variant has not previously been reported in somatic cancers (COSMIC). Experimental evidence: Deletion of N388/Y389 prevented SRA binding and enabled in-vitro lysis of T. b. rhodesiense in recombinant APOL1 assays. Based on available guidelines, this variant is considered to be a Variant of Uncertain Significance (VUS).
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.APOL1 encodes apolipoprotein L1, a secreted HDL-associated protein involved in lipid transport and reverse cholesterol transport. Certain inherited APOL1 variants increase the risk of chronic kidney disease, including focal segmental glomerulosclerosis and HIV-associated nephropathy, particularly in people with recent African ancestry. APOL1 is not established as a cancer-predisposition gene or a central driver of cancer.
The recorded framework is Generic ACMG/AMP 2015 with ClinGen SVI recommendations. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
The applied criteria and their strengths are shown as assessed under the stated framework.
Met at supporting strength: deletion of N388/Y389 prevented SRA binding and enabled in-vitro lysis of T. b. rhodesiense in recombinant APOL1 assays.
Met: the confirmed 6-bp in-frame deletion removes Asn388-Tyr389, producing a two-residue protein-length reduction outside an identified repeat region.
No benign criterion marked as applied in the recorded assessment.
VUS: PS3 (supporting) plus PM4 (supporting) do not satisfy any generic ACMG/AMP pathogenic, likely pathogenic, benign, or likely benign combination rule.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 11,305 / 1,612,914 alleles. Recorded AF 0.00700905. Recorded homozygote count 748.
This variant is present in gnomAD v2.1 (AF= 0.0130731; MAF= 1.30731%, 3662/280118 alleles, homozygotes = 226) and has highest observed frequency in the African/African American population (AF= 0.140185; MAF= 14.01846%, 3402/24268 alleles, homozygotes = 224); grpmax FAF= 0.135632.
This variant is present in gnomAD-Canada v1.0 (AF= 0.007057546145494028, 130/18420 alleles, homozygotes = 8).
Recorded SpliceAI maximum delta score: 0.001. Refer to the recorded PP3/BP4 rationale for interpretation.
2 risk factor · 2 Pathogenic · 1 Likely benign · 1 Benign · 1 Likely risk allele · 1 Pathogenic, low penetrance. ClinVar API review status: criteria provided, conflicting classifications.
No standalone functional evidence summary is recorded in evidence_summary.functional.
This variant has not previously been reported in somatic cancers (COSMIC).
This variant does not lie in a statistically significant hotspot.
ACMG/AMP criteria under Generic ACMG/AMP 2015 with ClinGen SVI recommendations, with the data and sources behind each one.
28 criteria with recorded statuses: 2 met · 5 not met · 11 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
No PS2, PM6, PP1, or BS4 evidence can be assigned because the available evidence contains cohort-level APOL1 risk-allele studies but no proband-level trio testing, family pedigree, informative meioses, or affected-relative segregation data.
The exact APOL1 G2 deletion shows case-control enrichment, but the computed exact-variant allele-frequency OR is approximately 1.69, below the generic PS4 threshold of >5.0.
No individual phenotype, alternate molecular diagnosis, or qualifying ClinVar expert-panel classification is documented for the remaining criteria.
PP3 and BP4 are both not applicable because this is an in-frame protein-length-changing deletion, not a missense, intronic, synonymous, or splice-region variant within the governing computational paths.
Population evidence demonstrates that APOL1 c.1164_1169del is a common African-ancestry G2 risk allele, not a rare disease allele: non-cancer grpmax FAF is 0.13536118 in gnomAD v2.1 and 0.13269198 in gnomAD v3.1, with numerous homozygotes.
The high frequency cannot be converted directly into BA1 or BS1 under the supplied generic defaults because published evidence supports a recessive, incomplete or low-penetrance APOL1 kidney-disease risk phenotype and the required maximum-credible-frequency inputs are unavailable.
PM2 is excluded by the observed population frequencies, while BS2 is not applicable because the full-penetrance early-age condition is not met.
No criteria match.
PS3 is met at supporting strength. The exact APOL1 G2 allele corresponding to NM_003661.4:c.1164_1169del (p.Asn388_Tyr389del) was tested in recombinant-protein and plasma trypanolysis assays with comparator proteins and parasite controls. The study reports that deletion of N388/Y389 was necessary and sufficient to prevent SRA binding and confer in-vitro lysis of T. b. rhodesiense, while the protein did not lyse T. b. gambiense. This is a reproducible, biologically relevant alteration of APOL1 function, but the evidence is not a validated clinical diagnostic assay and does not directly establish kidney-disease mechanism for this individual variant, so full strong PS3 is not assigned.
PS3: Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.
NM_003661.4:c.1164_1169del is a confirmed 6-bp in-frame deletion in the relevant MANE transcript, producing NP_003652.2:p.(Asn388_Tyr389del) and removing two amino acids from the protein. The variant is in exon 6 and is not a stop-loss change. The available evidence characterizes the affected APOL1 G2 region and does not identify the deleted segment as a repetitive protein region; therefore the generic PM4 definition for an in-frame deletion in a non-repeat region is met at supporting strength.
PM4: Protein length changes due to in-frame deletions/insertions in a non-repeat region or stop-loss variants.
PS4 is not met. PMID:20647424 directly studied the exact APOL1 G2 deletion, c.1164_1169del/p.(N388_Y389del), in 205 African-American FSGS cases and 180 controls and reported G2 allele frequencies of 23% versus 15%. Treating these rounded allele frequencies as approximate counts gives a case-control OR of 1.69 with an approximate Wald 95% CI of 1.17-2.45; I computed this OR and CI from the reported frequencies and cohort sizes. The reported OR 10.5 (95% CI 6.0-18.4) was for two APOL1 risk alleles versus zero or one, not for this exact variant alone. The governing PS4 threshold is OR >5.0 with a confidence interval excluding 1.0, so the exact-variant estimate does not satisfy PS4. PMID:21997394 also supports recessive association of G2 in case-control cohorts but does not provide an exact-variant OR exceeding 5.0 for the single G2 allele.
The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls. ... Note 1: Relative risk (RR) or odds ratio (OR), as obtained from case-control studies, is >5.0 and the confidence interval around the estimate of RR or OR does not include 1.0.
The variant is not absent or extremely rare in controls. The governing non-cancer sources report AF 0.00952617 with 131 homozygotes in gnomAD v2.1 exomes and AF 0.03957584 with 405 homozygotes in gnomAD v3.1 genomes. Both frequencies are far above the generic PM2 supporting threshold of 0.0001, so PM2 is not met.
PM2 (supporting): <= 0.0001 — SVI recommendation to downgrade PM2 to Supporting (ClinGen SVI 2020) (PMID:25741868).
PP5 is not met. ClinVar record 6081 has no expert-panel submissions and instead contains conflicting laboratory and aggregate assertions, including risk factor, Pathogenic, Likely benign, and Benign classifications. Under the supplied generic rule, ordinary laboratory submissions, aggregate labels, and non-expert assertions cannot trigger PP5.
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
The variant is an in-frame deletion, but BP3 requires an in-frame deletion in a repetitive region without a known function. The deleted APOL1 G2 segment, Asn388-Tyr389, has been directly characterized in association and functional studies, including effects on SRA interaction and parasite lysis, so the required absence of known function is not satisfied.
BP3: In frame-deletions/insertions in a repetitive region without a known function.
BP6 is not met. ClinVar record 6081 has no expert-panel submissions. Although individual laboratories submitted Benign and Likely benign classifications, the supplied generic rule restricts BP6 to an exact-variant ClinVar expert-panel benign or likely benign classification; ordinary laboratory submissions and aggregate labels cannot trigger BP6.
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
No case-level evidence documents that the APOL1 c.1164_1169del variant is de novo, confirms both maternity and paternity, establishes the proband's disease phenotype, or excludes a family history. The available literature concerns cohort-level APOL1 G2 risk-allele associations and does not provide parental testing for this proband.
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history.
PM3 is applicable because APOL1-associated kidney disease is described as recessive and the variant is an in-frame coding deletion, but the available evidence does not document an affected proband carrying this variant in trans with a pathogenic APOL1 variant. The literature describes G2-associated disease primarily with two APOL1 risk alleles or with G1, and population data show homozygotes, but neither establishes the required pathogenic-variant trans relationship or parental testing/phase for this case.
For recessive disorders, detected in trans with a pathogenic variant ... This requires testing of parents (or offspring) to determine phase.
No case-level evidence documents an assumed de novo occurrence of APOL1 c.1164_1169del in a patient with the disease. The available publications are cohort studies without a proband-specific de novo observation or parental testing information, so PM6 cannot be applied.
Assumed de novo, but without confirmation of paternity and maternity.
No family pedigree or genotype-phenotype segregation data are provided for APOL1 c.1164_1169del. The reviewed APOL1 publications are case-control or cohort studies and do not report multiple affected family members carrying the variant, so no segregation strength can be assigned.
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease. Note: May be used as stronger evidence with increasing segregation data.
PP4 cannot be assessed because the case materials do not provide an individual patient's phenotype or family history showing a highly specific disease presentation. Literature describing APOL1-associated FSGS or HIV-associated nephropathy is population-level evidence and cannot substitute for the patient's phenotype.
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
The required filtering frequencies exceed the generic BA1 threshold: gnomAD v2.1 non-cancer exomes report grpmax FAF 0.13536118 and gnomAD v3.1 non-cancer genomes report grpmax FAF 0.13269198, both based on populations with more than 2,000 observed alleles. However, this exact APOL1 G2 deletion is a documented African-ancestry kidney-disease risk allele with a recessive, incomplete or low-penetrance phenotype, and ClinVar classifications are conflicting, including risk factor and pathogenic, low penetrance. Because BA1 is stand-alone and a pathogenic disease association conflicts with a benign frequency conclusion, the generic 5% threshold alone is insufficient to apply BA1; an APOL1-specific maximum-credible-frequency analysis with prevalence, penetrance, and allelic-heterogeneity inputs is unavailable.
The required filtering frequencies exceed the generic BS1 default: gnomAD v2.1 non-cancer exomes grpmax FAF is 0.13536118 and gnomAD v3.1 non-cancer genomes grpmax FAF is 0.13269198, both from populations with more than 2,000 observed alleles. Nevertheless, the exact APOL1 G2 allele is an African-ancestry risk allele with a recessive, incomplete or low-penetrance kidney-disease association and substantial allelic heterogeneity. The supplied evidence lacks the disease prevalence, penetrance, inheritance-specific contribution, and allelic-heterogeneity inputs required for a Whiffin maximum-credible-frequency calculation, so the generic 1% default cannot establish BS1.
BS3 is not assessed because the available functional evidence does not show no damaging effect on APOL1 protein function or splicing. The reviewed study instead reports an altered trypanolytic phenotype for the exact N388/Y389 deletion, and no suitable benign functional assay with validated controls was identified.
BS3: Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
No affected family members, pedigree, or family genotyping results are documented. The available cohort studies do not establish that APOL1 c.1164_1169del fails to segregate with disease in an informative family, so lack of segregation cannot be assessed.
Lack of segregation in affected members of a family.
BP2 is applicable to the observed coding variant, but the available evidence does not document either required allelic configuration: this variant in trans with a pathogenic variant in a fully penetrant dominant gene/disorder, or this variant in cis with a pathogenic variant in any inheritance pattern. The reported APOL1 risk-allele observations and population homozygote counts do not establish cis/trans phase with a pathogenic variant.
Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
BP5 cannot be assessed because the case materials do not identify an alternate molecular basis for disease in the individual carrying this variant. Population and literature associations do not establish an alternate molecular diagnosis in this case.
Variant found in a case with an alternate molecular basis for disease.
PVS1 (ClinGen SVI PVS1 recommendations, PMC6185798, pvs1_generic_framework) applies only to null variant classes — nonsense, frameshift, canonical ±1/2 splice-consensus, translation-initiation-codon loss, and stop-loss variants — each expected to trigger nonsense-mediated decay or otherwise abolish normal protein function. NM_003661.4:c.1164_1169del in APOL1 is an in-frame insertion/deletion of undetermined repeat-region status predicted to produce NP_003652.2:p.(Asn388_Tyr389del). As a result, no null-variant mechanism (nonsense-mediated decay, truncation, or canonical splice disruption) is triggered by this variant class, so PVS1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PVS1 for APOL1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_null_variant_class
PS1 (Richards et al. 2015, PMID:25741868) requires the same amino acid change as a previously established pathogenic variant, evaluated regardless of the underlying nucleotide change. NM_003661.4:c.1164_1169del in APOL1 is an in-frame insertion/deletion of undetermined repeat-region status predicted to produce NP_003652.2:p.(Asn388_Tyr389del). As a result, no altered amino acid exists at this position to compare against any previously established pathogenic missense variant, so PS1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PS1 for APOL1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_missense
PM1 (Richards et al. 2015, PMID:25741868) applies to a missense variant located in a mutational hot spot and/or a critical, well-established functional domain without benign variation. NM_003661.4:c.1164_1169del in APOL1 is an in-frame insertion/deletion of undetermined repeat-region status predicted to produce NP_003652.2:p.(Asn388_Tyr389del). As a result, no altered residue exists to evaluate for mutational hot-spot or critical-domain membership, so PM1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PM1 for APOL1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_missense
PM5 (Richards et al. 2015, PMID:25741868) requires a novel missense change at an amino acid residue where a different missense change has previously been determined to be pathogenic. NM_003661.4:c.1164_1169del in APOL1 is an in-frame insertion/deletion of undetermined repeat-region status predicted to produce NP_003652.2:p.(Asn388_Tyr389del). As a result, no missense change exists at this residue to compare against a different pathogenic missense change at the same position, so PM5's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PM5 for APOL1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_missense
PP2 (Richards et al. 2015, PMID:25741868) applies to a missense variant in a gene with a low rate of benign missense variation, where missense variants are a common mechanism of disease. NM_003661.4:c.1164_1169del in APOL1 is an in-frame insertion/deletion of undetermined repeat-region status predicted to produce NP_003652.2:p.(Asn388_Tyr389del). As a result, the gene's missense-constraint properties are irrelevant because no missense change is present to evaluate, so PP2's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PP2 for APOL1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_missense
PP3 is not applicable because the variant is a 6-bp in-frame deletion, NM_003661.4:c.1164_1169del, predicted to produce NP_003652.2:p.(Asn388_Tyr389del). The governing generic scope limits PP3/BP4 to missense variants using REVEL or intronic, synonymous, or splice-region variants using SpliceAI; this in-frame protein-length-changing variant is outside both permitted paths. Therefore the available SpliceAI max delta score of 0.001 is not evaluated as PP3 evidence, and no REVEL or SpliceAI result can establish PP3 for this variant.
PP3: Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.). ... PP3/BP4 apply only to a missense variant, or to a splice-region/intronic variant via the SpliceAI path - never to a frameshift, nonsense, or other truncating/protein-length-changing variant.
The variant is observed in homozygotes, including 131 homozygotes in gnomAD v2.1 non-cancer exomes and 405 in gnomAD v3.1 non-cancer genomes. However, BS2 applies only when a healthy adult observation is relevant to a recessive disorder with full penetrance expected at an early age. APOL1 G2 is associated with a recessive kidney-disease risk phenotype with incomplete, age-dependent, or stress-dependent expression, so population homozygotes do not satisfy BS2's applicability condition.
Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
BP1 (Richards et al. 2015, PMID:25741868) applies to a missense variant in a gene for which primarily truncating variants are known to cause disease. NM_003661.4:c.1164_1169del in APOL1 is an in-frame insertion/deletion of undetermined repeat-region status predicted to produce NP_003652.2:p.(Asn388_Tyr389del). As a result, the gene's truncating-variant mechanism is irrelevant because no missense change is present to evaluate, so BP1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP1 for APOL1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_missense
BP4 is not applicable because the variant is a 6-bp in-frame deletion, NM_003661.4:c.1164_1169del, predicted to produce NP_003652.2:p.(Asn388_Tyr389del). The governing generic scope limits PP3/BP4 to missense variants using REVEL or intronic, synonymous, or splice-region variants using SpliceAI; this in-frame protein-length-changing variant is outside both permitted paths. A SpliceAI max delta score of 0.001 therefore cannot support BP4 for this variant, even though it is below the generic SpliceAI BP4 supporting threshold of 0.1.
BP4: Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc) ... PP3/BP4 apply only to a missense variant, or to a splice-region/intronic variant via the SpliceAI path - never to a frameshift, nonsense, or other truncating/protein-length-changing variant.
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_003661.4:c.1164_1169del in APOL1 is an in-frame insertion/deletion of undetermined repeat-region status predicted to produce NP_003652.2:p.(Asn388_Tyr389del). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for APOL1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
Every interpreted variant in APOL1, mapped onto the exon structure of NM_003661.4. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| African/African American10174 / 74,912 | 0.14724 hom |
| Remaining individuals535 / 62,448 | 0.008617 hom |
| Admixed American501 / 59,898 | 0.00847 hom |
| Middle Eastern16 / 6,056 | 0.0026 |
| South Asian25 / 90,892 | 0.00028 |
| European (non-Finnish)54 / 1,179,462 | 4.6e-05 |
| African/African American3402 / 24,268 | 0.14224 hom |
| Admixed American202 / 35,278 | 0.00571 hom |
| Remaining individuals36 / 7,140 | 0.0051 hom |
| South Asian10 / 30,358 | 0.00033 |
| Ashkenazi Jewish1 / 10,206 | 9.8e-05 |
| European (non-Finnish)11 / 127,950 | 8.6e-05 |
This variant is present in gnomAD v4.1 (AF= 0.00700905; MAF= 0.70091%, 11305/1612914 alleles, homozygotes = 748) and has highest observed frequency in the African/African American population (AF= 0.135813; MAF= 13.58127%, 10174/74912 alleles, homozygotes = 724); grpmax FAF= 0.133605.
This variant is present in gnomAD v2.1 (AF= 0.0130731; MAF= 1.30731%, 3662/280118 alleles, homozygotes = 226) and has highest observed frequency in the African/African American population (AF= 0.140185; MAF= 14.01846%, 3402/24268 alleles, homozygotes = 224); grpmax FAF= 0.135632.
This variant is present in gnomAD-Canada v1.0 (AF= 0.007057546145494028, 130/18420 alleles, homozygotes = 8).
PP3 is not applicable because the variant is a 6-bp in-frame deletion, NM_003661.4:c.1164_1169del, predicted to produce NP_003652.2:p.(Asn388_Tyr389del). The governing generic scope limits PP3/BP4 to missense variants using REVEL or intronic, synonymous, or splice-region variants using SpliceAI; this in-frame protein-length-changing variant is outside both permitted paths. Therefore the available SpliceAI max delta score of 0.001 is not evaluated as PP3 evidence, and no REVEL or SpliceAI result can establish PP3 for this variant.
PP3: Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.). ... PP3/BP4 apply only to a missense variant, or to a splice-region/intronic variant via the SpliceAI path - never to a frameshift, nonsense, or other truncating/protein-length-changing variant.
BP4 is not applicable because the variant is a 6-bp in-frame deletion, NM_003661.4:c.1164_1169del, predicted to produce NP_003652.2:p.(Asn388_Tyr389del). The governing generic scope limits PP3/BP4 to missense variants using REVEL or intronic, synonymous, or splice-region variants using SpliceAI; this in-frame protein-length-changing variant is outside both permitted paths. A SpliceAI max delta score of 0.001 therefore cannot support BP4 for this variant, even though it is below the generic SpliceAI BP4 supporting threshold of 0.1.
BP4: Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc) ... PP3/BP4 apply only to a missense variant, or to a splice-region/intronic variant via the SpliceAI path - never to a frameshift, nonsense, or other truncating/protein-length-changing variant.
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_003661.4:c.1164_1169del in APOL1 is an in-frame insertion/deletion of undetermined repeat-region status predicted to produce NP_003652.2:p.(Asn388_Tyr389del). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for APOL1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
9 paper records listed. 2 cited in the classification.
Deletion of N388/Y389 was necessary and sufficient to prevent interaction with SRA and to confer on ApoL1 the ability to lyse T.b. rhodesiense in vitro.
Location Results, functional ApoL1 assays; Figure 3C and Table 1
Context Association analyses in African-American cohorts plus in-vitro lysis assays using human plasma and recombinant ApoL1 proteins against T. b. brucei, T. b. rhodesiense, and T. b. gambiense.
G2, which has a 6 base pair (bp) in-frame deletion (N388del:Y389del)
Location Introduction, paragraph 1; Results, Table 2 and surrounding text; Discussion, final paragraph
Context Case-control analysis of 217 African American primary FSGS cases, 54 biopsy-proven HIV-associated collapsing glomerulopathy cases, and African American control groups; APOL1 variants were genotyped using TaqMan assays, including the G2 indel rs71785313.
When testing the T.b. rhodesiense SRA+ resistant clones, only APOL1 G1 and G2 isoforms could lyse the parasite, indicating that G0, G3, p.K150, and p.K264 isoforms could not overcome the SRA-driven APOL1 restriction.
Results, Association of common and rare APOL1 variants with FSGS/HIVAN; Results, Population genetics of APOL1 variants and haplotypes; Results, Trypanolytic potential of APOL1 isoforms
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The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
This variant is present in gnomAD v4.1 (AF= 0.00700905; MAF= 0.70091%, 11305/1612914 alleles, homozygotes = 748) and has highest observed frequency in the African/African American population (AF= 0.135813; MAF= 13.58127%, 10174/74912 alleles, homozygotes = 724); grpmax FAF= 0.133605.
This variant is present in gnomAD v2.1 (AF= 0.0130731; MAF= 1.30731%, 3662/280118 alleles, homozygotes = 226) and has highest observed frequency in the African/African American population (AF= 0.140185; MAF= 14.01846%, 3402/24268 alleles, homozygotes = 224); grpmax FAF= 0.135632.
This variant is present in gnomAD-Canada v1.0 (AF= 0.007057546145494028, 130/18420 alleles, homozygotes = 8).
This variant has been reported in ClinVar as risk factor (2 clinical laboratories) and as Pathogenic (2 clinical laboratories) and as Likely benign (1 clinical laboratory) and as Benign (1 clinical laboratory) and as Likely risk allele (1 clinical laboratory) and as Pathogenic, low penetrance (1 clinical laboratory). (ClinVarID = 6081)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
This variant does not lie in a statistically significant hotspot.