The APOL1 NM_003661.4:c.1024A>G (NP_003652.2:p.(Ser342Gly)) missense variant has not previously been reported in somatic cancers (COSMIC). 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.
No pathogenic criterion marked as applied in the recorded assessment.
Met, supporting: missense REVEL score 0.081 is below the generic BP4 supporting cutoff of 0.29.
VUS: BP4 supporting from REVEL 0.081 is the only applied criterion and does not satisfy a generic ACMG 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: 18,406 / 1,614,072 alleles. Recorded AF 0.0114035. Recorded homozygote count 2158.
This variant is present in gnomAD v2.1 (AF= 0.0211138; MAF= 2.11138%, 5970/282754 alleles, homozygotes = 689) and has highest observed frequency in the African/African American population (AF= 0.227568; MAF= 22.75682%, 5671/24920 alleles, homozygotes = 687); grpmax FAF= 0.225318.
Not available in gnomAD-Canada v1.0.
Recorded REVEL score: 0.081. Refer to the recorded PP3/BP4 rationale for interpretation.
2 risk factor · 1 Likely risk allele · 1 Uncertain significance · 1 Pathogenic · 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: 1 met · 8 not met · 14 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
For the requested codon, residue, domain, and missense-mechanism criteria, no criterion is met: PS1 and PM5 lack the required distinct comparator variants, PM1 lacks sufficiently established domain-without-benign-variation or hotspot evidence, and PP2/BP1 lack required gene-wide premises.
No proband-parent de novo observation, assumed-de-novo report, or family pedigree with informative segregation or non-segregation is available for this variant.
PS3 and BS3 were not assessed because the available studies do not provide a sufficiently validated, reproducible, variant-specific functional result for APOL1 S342G alone.
PS4 is not met because the exact S342G-only case-control estimate is OR 2.32 with 95% CI 0.81-6.69, failing both the OR >5.0 and CI-not-including-1.0 requirements.
PP4 and BP5 remain not assessed because the case materials do not provide the individual phenotype/family history or an alternate molecular diagnosis.
PP5 and BP6 are not met because ClinVar has conflicting laboratory submissions and no exact-variant expert-panel classification.
The variant is a missense substitution, so the generic PP3/BP4 assessment uses REVEL only; the SpliceAI score is not used for these criteria.
REVEL 0.081 does not meet PP3 supporting (>=0.644) and meets BP4 supporting (<=0.29).
Population evidence supports that APOL1 p.Ser342Gly is a common African-ancestry-enriched risk allele, not a rare variant suitable for PM2.
The high filtering frequency exceeds generic BA1 and BS1 defaults, but those criteria are not assessed because the allele has a documented recessive, incompletely penetrant, conditional kidney-disease association and lacks a disorder-specific maximum-credible-frequency calculation.
BS2 is not applicable because the governing rule requires full penetrance expected at an early age, which is inconsistent with the APOL1 risk-disease context.
No criteria match.
Scope was settled first under the generic rule: this is a missense substitution, NM_003661.4:c.1024A>G, NP_003652.2:p.(Ser342Gly), so BP4 uses the REVEL path only; SpliceAI is not used for this missense BP4 assessment. REVEL is 0.081, at or below the generic BP4 supporting cutoff of <=0.29, so BP4 is met at supporting strength. The same REVEL prediction is not counted again for PP3.
BP4 (supporting): <= 0.29 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
The variant is APOL1 p.Ser342Gly (c.1024A>G; rs73885319), and the reviewed literature documents this same nucleotide change, but no distinct nucleotide substitution producing the same amino-acid change was identified. Therefore, the required PS1 comparator is absent; observations of the queried variant itself do not satisfy PS1.
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change.
The exact S342G-only haplotype was reported in 7 of 271 African American cases and 7 of 620 African American controls in Kopp et al. (PMID:21997394). Treating these as a case-control comparison, the calculated odds ratio is (7/264)/(7/613) = 2.32 with an approximate 95% CI of 0.81-6.69. The governing ACMG/AMP threshold is OR >5.0 with a confidence interval that does not include 1.0; the explicit comparison is 2.32 > 5.0? no, and 0.81-6.69 excludes 1.0? no. Therefore PS4 is not met. The same paper's broader G1/G2 results concern risk-allele genotypes or haplotypes rather than an isolated S342G estimate and do not establish the required exact-variant threshold.
The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls. ... 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.
No VCEP covers APOL1 and vcep_materials.json contains no domain table. The literature places S342G in or near the APOL1 SRA-interacting region, but the available evidence does not establish a complete, residue-bounded critical domain without benign variation, and the hotspot searches were negative. The generic PM1 requirement is therefore not met.
Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation.
PM2 is not met because the variant is common in population controls. The supplied generic supporting threshold is allele frequency <=0.0001, whereas applicable all-comers gnomAD values are 0.0211138 in v2.1 and 0.0114035 in v4.1. The gnomAD v2.1 non-cancer exome-only subset also contains the variant at AF 0.0158214 (3748/236894 alleles; 447 homozygotes), so the specified subset does not restore rarity.
PM2: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium. ... PM2 (supporting): <= 0.0001 — SVI recommendation to downgrade PM2 to Supporting (ClinGen SVI 2020) (PMID:25741868)
The queried variant changes Ser342 to Gly. The reviewed evidence identifies S342G itself and no different missense substitution at residue 342 that has been established as pathogenic. The PM5 same-residue comparator requirement is therefore not met.
Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before.
Scope was settled first under the generic rule: this is a missense substitution, NM_003661.4:c.1024A>G, NP_003652.2:p.(Ser342Gly), so PP3 uses the REVEL path only; SpliceAI is not used for this missense PP3/BP4 assessment, and BayesDel has no established generic ACMG-strength calibration. REVEL is 0.081, which is below the generic PP3 supporting threshold of >=0.644, so PP3 is not met. The low REVEL score is instead considered under BP4 without double-counting it.
PP3 (supporting): >= 0.644 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
ClinVar contains conflicting laboratory submissions for the exact variant, including risk factor, likely risk allele, uncertain significance, pathogenic, and pathogenic low penetrance, but no expert-panel submission. The available pathogenic assertions are ordinary laboratory submissions and do not satisfy the required exact-variant reputable-source condition for PP5 under the stated generic rule.
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
ClinVar contains conflicting laboratory submissions for the exact variant and no expert-panel submission. There is no exact-variant expert-panel benign or likely benign classification; therefore ordinary laboratory submissions and the conflicting aggregate record cannot trigger BP6 under the stated generic rule.
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
No proband-level case report or pedigree evidence documents this variant as de novo, and there is no confirmation of both maternity and paternity or documentation of no family history. The available literature concerns population association and functional studies rather than a de novo clinical observation.
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history.
The available functional literature is suggestive but does not establish a well-established, reproducible, variant-specific damaging assay result sufficient for PS3. PMID:20647424 directly tested S342G in recombinant ApoL1 assays and found that S342G alone was less lytic than the combined S342G/I384M G1 protein, with maximal lysis requiring the combined allele; the assay therefore does not isolate a clear disease-damaging effect of c.1024A>G. PMID:25853332 reports, in a review of prior work, that S342G-containing G1G can kill Trypanosoma brucei in vivo, but this is not a new validated experiment and trypanolysis is not by itself an established assay for the kidney-disease mechanism. PMID:32675303 reports dose-dependent toxicity and loss of viability for the combined G1 S342G/I384M haplotype in HEK293 cells, not for the queried S342G substitution alone. No validated clinical-laboratory assay, definitive assay calibration, or sufficiently specific control framework was identified. Accordingly, the evidence cannot be calibrated as PS3 at any strength under the generic rule.
PS3
PM3 cannot be assessed because the available evidence does not document the queried APOL1 p.Ser342Gly allele in trans with a pathogenic variant in an affected proband, nor does it provide parent or offspring testing establishing phase. The literature identifies p.Ser342Gly as part of the G1 haplotype with p.Ile384Met and reports a rare p.Ser342Gly-only haplotype, but it does not establish a qualifying pathogenic variant in trans for this case.
For recessive disorders, detected in trans with a pathogenic variant ... This requires testing of parents (or offspring) to determine phase.
No clinical report documents this variant as assumed de novo. The available evidence does not provide a proband with the relevant disease, parental testing information, or a statement that maternity and paternity were unconfirmed.
Assumed de novo, but without confirmation of paternity and maternity.
No family pedigree or genotype-phenotype segregation series is documented for this variant. PMID:21997394 reports S342G-only haplotypes in seven cases and seven controls in a case-control study, not multiple affected family members with informative meioses; therefore, PP1 cannot be assessed from that study.
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease. ... May be used as stronger evidence with increasing segregation data.
The case documents important APOL1 missense risk alleles and functional effects, but it does not provide a gene-wide estimate demonstrating a low rate of benign missense variation. Because that required gene-level premise cannot be established from the supplied evidence, PP2 is not assessed.
Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
No individual case phenotype or family history is supplied for this interpretation. The available literature describes APOL1 S342G/G1 as a kidney-disease risk allele associated with heterogeneous conditions including FSGS and HIVAN, rather than documenting that this patient's phenotype is highly specific for a disease with a single genetic etiology. The criterion cannot be assessed without the patient's phenotype and relevant differential diagnosis.
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
The required filtering frequency exceeds the generic BA1 threshold: gnomAD v2.1 grpmax FAF is 0.225318 and gnomAD v4.1 grpmax FAF is 0.225877, both from African/African American samples with more than 2,000 observed alleles. BA1 is not assessed because APOL1 p.Ser342Gly is the G1 risk allele with a documented recessive, incompletely penetrant and conditional kidney-disease association, and ClinVar classifications conflict, including risk factor, likely risk allele, pathogenic and pathogenic low penetrance. Applying a stand-alone benign conclusion from the generic 5% threshold would be unsafe without a disorder-specific maximum-credible-frequency calculation and resolution of the disease-associated risk interpretation.
BA1 (stand-alone): >= 0.05 — ACMG/AMP 2015 stand-alone benign allele frequency (PMID:25741868)
The generic BS1 default is exceeded by the filtering frequency: grpmax FAF is 0.225318 in gnomAD v2.1 and 0.225877 in gnomAD v4.1, with the elevated frequency concentrated in African/African American samples exceeding 2,000 observed alleles. BS1 is not assessed from the default 1% threshold alone because APOL1 G1 is an established recessive, incompletely penetrant and environmentally conditional kidney-disease risk allele, so the high ancestry-enriched frequency may be compatible with disease risk. No disorder-specific maximum-credible-frequency calculation using prevalence, penetrance and allelic heterogeneity is available.
BS1 (strong): >= 0.01 — Generic SVI default; per-gene derivation preferred (Whiffin et al. 2017) (PMID:28518168)
No well-established functional study demonstrating that APOL1 S342G has no damaging effect on protein function or splicing was identified. PMID:20647424 reported reduced trypanolytic activity for S342G alone relative to the combined G1 protein, but this is not a benign functional result and does not establish normal protein function or normal splicing. The other reviewed functional sources describe either S342G-containing G1 activity or the combined S342G/I384M haplotype and do not support a benign interpretation. Therefore BS3 is not assessed rather than applied or rejected on the basis of an inadequate negative assay.
BS3
No affected family members and no family genotype-phenotype analysis are documented, so lack of segregation cannot be evaluated. PMID:21997394 and PMID:25993319 are cohort studies rather than pedigrees; their case-control or aggregate association results do not establish non-segregation in affected relatives, and no family-level phenocopy assessment is provided.
Lack of segregation in affected members of a family. ... Caveat: The presence of phenocopies for common phenotypes (i.e. cancer, epilepsy) can mimic lack of segregation among affected individuals.
The supplied evidence documents APOL1 missense risk alleles and does not establish that APOL1 disease is caused primarily by truncating variants. However, it also does not provide a systematic gene-wide variant spectrum sufficient to make the converse conclusion under BP1, so the criterion is not assessed.
Missense variant in a gene for which primarily truncating variants are known to cause disease.
BP2 cannot be assessed because the available evidence does not establish that APOL1 p.Ser342Gly is observed in trans with a pathogenic variant in a fully penetrant dominant disorder, or in cis with an independently qualifying pathogenic variant. The reports describe p.Ser342Gly in cis with p.Ile384Met as the G1 haplotype and also describe p.Ser342Gly alone, but they do not establish p.Ile384Met as a pathogenic variant under the governing BP2 definition or provide a qualifying dominant-disorder observation.
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.
No case-level information documents that the variant was found in a patient with an alternate molecular basis for disease. The population and literature sources describe APOL1 risk associations but do not establish an alternate molecular diagnosis for the present case, so BP5 cannot be adjudicated.
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.1024A>G in APOL1 is a missense substitution predicted to produce NP_003652.2:p.(Ser342Gly). 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
PM4 (Richards et al. 2015, PMID:25741868) applies to protein length changes: in-frame insertions/deletions in a non-repetitive region, or stop-loss variants that extend the protein past the reference stop codon. NM_003661.4:c.1024A>G in APOL1 is a missense substitution predicted to produce NP_003652.2:p.(Ser342Gly). As a result, no change in protein length occurs, so there is nothing for this criterion to evaluate, so PM4's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PM4 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_stop_loss_or_nonrepeat_indel
BS2 is not applicable because its governing definition requires observation in a healthy adult for a disorder with full penetrance expected at an early age. APOL1 G1-associated kidney disease is described as recessive, incompletely penetrant and conditional on additional environmental or cellular stressors. gnomAD documents many homozygotes (689 in v2.1 and 2,158 in v4.1), but these database observations do not establish healthy-adult status or full early-age penetrance and therefore cannot satisfy BS2.
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.
BP3 (Richards et al. 2015, PMID:25741868) applies to in-frame insertions/deletions located in a repetitive region without a known function. NM_003661.4:c.1024A>G in APOL1 is a missense substitution predicted to produce NP_003652.2:p.(Ser342Gly). As a result, the variant does not alter protein length within a repeat region, so there is nothing for this criterion to evaluate, so BP3's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP3 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_repeat_region_indel
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.1024A>G in APOL1 is a missense substitution predicted to produce NP_003652.2:p.(Ser342Gly). 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 American17142 / 74,940 | 0.232135 hom |
| Remaining individuals645 / 62,508 | 0.0118 hom |
| Admixed American527 / 60,022 | 0.00884 hom |
| Middle Eastern9 / 6,062 | 0.00151 hom |
| South Asian14 / 91,076 | 0.00015 |
| European (non-Finnish)69 / 1,180,036 | 5.8e-05 |
| African/African American5671 / 24,920 | 0.23687 hom |
| Admixed American240 / 35,438 | 0.00681 hom |
| Remaining individuals42 / 7,214 | 0.00581 hom |
| European (non-Finnish)14 / 129,126 | 0.00011 |
| South Asian3 / 30,616 | 9.8e-05 |
This variant is present in gnomAD v4.1 (AF= 0.0114035; MAF= 1.14035%, 18406/1614072 alleles, homozygotes = 2158) and has highest observed frequency in the African/African American population (AF= 0.228743; MAF= 22.87430%, 17142/74940 alleles, homozygotes = 2135); grpmax FAF= 0.225877.
This variant is present in gnomAD v2.1 (AF= 0.0211138; MAF= 2.11138%, 5970/282754 alleles, homozygotes = 689) and has highest observed frequency in the African/African American population (AF= 0.227568; MAF= 22.75682%, 5671/24920 alleles, homozygotes = 687); grpmax FAF= 0.225318.
Not available in gnomAD-Canada v1.0.
Scope was settled first under the generic rule: this is a missense substitution, NM_003661.4:c.1024A>G, NP_003652.2:p.(Ser342Gly), so BP4 uses the REVEL path only; SpliceAI is not used for this missense BP4 assessment. REVEL is 0.081, at or below the generic BP4 supporting cutoff of <=0.29, so BP4 is met at supporting strength. The same REVEL prediction is not counted again for PP3.
BP4 (supporting): <= 0.29 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
Scope was settled first under the generic rule: this is a missense substitution, NM_003661.4:c.1024A>G, NP_003652.2:p.(Ser342Gly), so PP3 uses the REVEL path only; SpliceAI is not used for this missense PP3/BP4 assessment, and BayesDel has no established generic ACMG-strength calibration. REVEL is 0.081, which is below the generic PP3 supporting threshold of >=0.644, so PP3 is not met. The low REVEL score is instead considered under BP4 without double-counting it.
PP3 (supporting): >= 0.644 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
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.1024A>G in APOL1 is a missense substitution predicted to produce NP_003652.2:p.(Ser342Gly). 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 = 0.01). REVEL score = 0.081. BayesDel score = -0.733948.
8 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
The strongest signal was obtained for a two-locus allele, termed G1, consisting of the two derived nonsynonymous coding variants rs73885319 [S342→G342 (S342G) (15)] and rs60910145 (I384M) in the last exon of APOL1.
Results, initial FSGS association analysis; Results, recombinant ApoL1 functional assays (Fig. 3C)
the G1GM/GG* association strongly suggests that the single G1S342G allele determines the G1 pathogenic phenotype
Results, paragraph beginning 'Among African American subjects'; Table 2; Discussion
The G1 allele is composed of two SNPs in near-perfect linkage disequilibrium (G1G, p.S342G and G1M, p.I384M) but only G1G can kill trypanosome in vivo.
Section 'APOL1 and resistance to trypanosome infection,' paragraph discussing the APOL1 G1 and G2 renal risk alleles
We exhaustively analyzed 33 rare and common variants using association analyses, gene-set analyses and compound heterozygous complementation of a single G1 or G2 risk allele analyses, but found no evidence of association with FSGS/HIVAN for other APOL1 variants.
Discussion, paragraph 1
Similar to the SRA protein, the variants G1 and G2 have a similar diminished capacity to bind VAMP8 in human cells.
Loss-of-function section, lines 242-250
Mechanisms by which two coding variants (G1, S342G/I384M and G2, del388N389Y) of the APOL1 gene contribute to the excess rate of non-diabetic ESKD
Introduction; Results sections describing monoallelic and biallelic APOL1 G0/G1/G2 expression
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
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= 0.0114035; MAF= 1.14035%, 18406/1614072 alleles, homozygotes = 2158) and has highest observed frequency in the African/African American population (AF= 0.228743; MAF= 22.87430%, 17142/74940 alleles, homozygotes = 2135); grpmax FAF= 0.225877.
This variant is present in gnomAD v2.1 (AF= 0.0211138; MAF= 2.11138%, 5970/282754 alleles, homozygotes = 689) and has highest observed frequency in the African/African American population (AF= 0.227568; MAF= 22.75682%, 5671/24920 alleles, homozygotes = 687); grpmax FAF= 0.225318.
Not available in gnomAD-Canada v1.0.
This variant has been reported in ClinVar as risk factor (2 clinical laboratories) and as Likely risk allele (1 clinical laboratory) and as Uncertain significance (1 clinical laboratory) and as Pathogenic (1 clinical laboratory) and as Pathogenic, low penetrance (1 clinical laboratory). (ClinVarID = 277678)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.081. BayesDel score = -0.733948.
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.