The APOE NM_000041.4:c.388T>C (NP_000032.1:p.(Cys130Arg)) missense variant has previously been reported in somatic cancers (COSMIC; COSV52985231, n = 14 times). Based on available guidelines, this variant is considered to be Benign.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign classification under the recorded framework.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.APOE encodes apolipoprotein E, which helps the liver and other cells clear triglyceride-rich lipoprotein remnants from the blood. Changes in this gene can cause familial dysbetalipoproteinemia (type III hyperlipoproteinemia), leading to increased cholesterol and triglyceride levels. APOE has no established cancer role based on the available information.
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: gnomAD total allele frequency is 0.148520, exceeding the BA1 stand-alone threshold of 0.05.
Met at supporting strength: REVEL 0.229 is within the generic BP4 supporting threshold of <= 0.29 for this missense variant.
Benign: BA1 stand-alone benign is met by gnomAD AF 0.148520, with additional BP4 supporting evidence from REVEL 0.229 under generic ACMG rules.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 232,864 / 1,567,892 alleles. Recorded AF 0.14852. Recorded homozygote count 17710.
This variant is present in gnomAD v2.1 (AF= 0.142529; MAF= 14.25294%, 28637/200920 alleles, homozygotes = 2091) and has highest observed frequency in the African/African American population (AF= 0.218158; MAF= 21.81583%, 3871/17744 alleles, homozygotes = 403); grpmax FAF= 0.215746.
This variant is present in gnomAD-Canada v1.0 (AF= 0.12580154331050972, 2315/18402 alleles, homozygotes = 168).
Recorded REVEL score: 0.229. Refer to the recorded PP3/BP4 rationale for interpretation.
5 Uncertain significance · 2 risk factor · 2 Likely pathogenic · 2 Pathogenic · 1 Established risk allele · 1 other · 1 Benign · 1 Likely benign · 1 Likely risk allele. ClinVar API review status: criteria provided, conflicting classifications.
No standalone functional evidence summary is recorded in evidence_summary.functional.
This variant has previously been reported in somatic cancers (COSMIC; COSV52985231, n = 14 times).
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 · 8 not met · 13 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
For APOE p.Cys130Arg, PM1, PP2, and BP1 are not met because the common missense variant and APOE disease context do not satisfy their prerequisites; PS1 and PM5 remain not assessed without validated pathogenic comparator variants.
No segregation or de novo criterion is assessed because the available evidence lacks proband phenotype, pedigree, parental testing, affected-relative testing, and informative meioses.
No VCEP covers APOE in this case; generic ACMG/AMP 2015 rules govern.
The exact variant is NM_000041.4:c.388T>C (NP_000032.1:p.Cys130Arg).
The literature_pass packet contains no ai_classified_papers; relevant available full-text extracts were checked before concluding that no exact-variant PS4 case-control evidence was demonstrated.
PP5 and BP6 were not triggered because the ClinVar audit reports zero expert-panel submissions and the pathogenic/benign assertions are ordinary laboratory submissions.
Population evidence is strongly benign for BA1 and contradicts PM2 because the variant is common and has numerous homozygotes in gnomAD.
BS1 is not assigned from the generic 1% default because APOE-associated Alzheimer disease risk is late-onset and incompletely penetrant; a disorder-specific maximum credible allele frequency calculation is required.
BS2 is not assessed because aggregate gnomAD homozygote counts do not establish healthy adult status or early-age full penetrance.
No criteria match.
BA1 is met. The variant has gnomAD v2.1 total allele frequency 0.142529 (28,637/200,920 alleles; 2,091 homozygotes) and gnomAD v4.1 total allele frequency 0.148520 (232,864/1,567,892 alleles; 17,710 homozygotes). Both substantially exceed the generic ACMG/AMP stand-alone threshold of 0.05. The highest observed population frequencies are also very high (0.218158 in African/African American individuals in v2.1 and 0.220463 in v4.1), with no indication that the result is a sequencing-quality artifact.
Allele frequency is above 5% in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
NM_000041.4:c.388T>C is a missense variant, NP_000032.1:p.(Cys130Arg), so the governing generic path is REVEL only; SpliceAI is not used for PP3/BP4 in this missense situation. The REVEL score is 0.229, which meets the generic BP4 supporting threshold of <= 0.29. This is a single applicable predictor path, without double-counting SpliceAI or using the uncalibrated BayesDel score.
Missense variant -> REVEL only. Its SpliceAI score says nothing about whether the amino-acid substitution is tolerated, so 'no predicted splice impact' is never BP4 support for a missense variant. ... BP4 (supporting): <= 0.29 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
The generic PS4 definition requires a significantly increased prevalence in affected individuals compared with controls, with an odds ratio or relative risk >5.0 and a confidence interval excluding 1.0. The literature_pass packet has no ai_classified_papers, and the reviewed full texts do not report exact APOE NM_000041.4:c.388T>C (p.Cys130Arg) case and control counts, a case-control odds ratio, or a confidence interval. PMID:11940689 studied APOE genotype and recovery after traumatic brain injury without variant-specific case-control data; PMID:15668424 studied common APOE codon-112/158 genotypes rather than p.Cys130Arg; PMID:20298421 discusses APOE epsilon4 generally; PMID:21900891 and PMID:26186657 concern CYP2C9/VKORC1 warfarin pharmacogenetics; and PMID:23060451 studied APOE isoforms in mice. Therefore no qualifying exact-variant case-control enrichment is demonstrated, and no odds ratio or confidence interval can be computed from the available evidence.
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.
APOE has no VCEP coverage and vcep_materials.json contains no authoritative domain-table entry. The supplied hotspot result reports no statistically significant hotspot for APOE C130, and the variant is common in gnomAD v4.1 (AF 0.148520; African/African American AF 0.220463; 17,710 homozygotes), which is inconsistent with a critical domain or hotspot without benign variation. No qualifying generic ACMG PM1 site is established by the supplied evidence.
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. The variant is common in population controls: gnomAD v2.1 total AF is 0.142529 (28,637/200,920 alleles; 2,091 homozygotes), and gnomAD v4.1 total AF is 0.148520 (232,864/1,567,892 alleles; 17,710 homozygotes). These frequencies are far above the supplied generic PM2 supporting threshold of <=0.0001 and are incompatible with absence or extremely low frequency in controls.
Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
PP2 requires both a low rate of benign missense variation and missense variants as a common disease mechanism. APOE p.Cys130Arg is common in gnomAD v4.1 (AF 0.148520; 17,710 homozygotes), demonstrating abundant common missense variation inconsistent with the low-benign-missense prerequisite; the supplied literature also describes APOE epsilon4 as a common risk allele rather than a rare missense mechanism. PP2 is therefore not met.
Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
NM_000041.4:c.388T>C is a missense variant, NP_000032.1:p.(Cys130Arg), so the governing generic path is REVEL only; SpliceAI is not used for PP3/BP4 in this missense situation. The REVEL score is 0.229, below the generic PP3 supporting threshold of >= 0.644. BayesDel is not used because no generic ACMG-strength calibration is established.
Missense variant -> REVEL only. Its SpliceAI score says nothing about whether the amino-acid substitution is tolerated, so 'no predicted splice impact' is never BP4 support for a missense variant. ... PP3 (supporting): >= 0.644 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
PP5 requires a reputable source to recently report the exact variant as pathogenic when the underlying evidence is unavailable for independent evaluation. ClinVar reports conflicting laboratory classifications, has no expert-panel submission, and has zero usable expert-panel or criterion-lead submissions in the audit. The pathogenic and likely pathogenic entries are ordinary laboratory submissions, not an expert-panel assertion, and the reviewed publications do not independently report this exact variant as pathogenic.
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
BP1 requires a gene for which primarily truncating variants are known to cause disease. The available APOE-specific literature instead describes the common missense epsilon4 allele as an Alzheimer disease risk factor, neither necessary nor sufficient for disease, and does not establish a primarily truncating disease mechanism. BP1 is not met.
Missense variant in a gene for which primarily truncating variants are known to cause disease.
BP6 requires a reputable source to recently report the exact variant as benign when the evidence is unavailable for independent evaluation. ClinVar shows a benign and a likely benign laboratory submission, but no expert-panel submission and no usable expert-panel or criterion-lead assertion; the record is conflicting and therefore does not meet the required exact-variant expert-panel condition.
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
The variant is APOE NM_000041.4:c.388T>C, p.Cys130Arg. The available ClinVar record is conflicting and has no expert-panel submission; it does not establish a previously established pathogenic variant with the same amino-acid change, and no alternate nucleotide change producing p.Cys130Arg was documented in the supplied evidence. Therefore the evidence is insufficient to assess PS1 rather than to apply it.
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change. ... Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.
PS2 cannot be assessed because the available case evidence does not document a proband with the relevant disease, absence of family history, or confirmed maternity and paternity for NM_000041.4:c.388T>C. No pedigree or parental testing results establish that the variant is de novo.
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history.
PS3 cannot be assessed because no validated in vitro or in vivo functional study in the reviewed evidence directly tests APOE NM_000041.4:c.388T>C (p.Cys130Arg). The APOE4 transgenic-mouse study (PMID:23060451) compares APOE2, APOE3, and APOE4 isoforms and reports amyloid-beta phenotypes, but it does not mention or assay p.Cys130Arg; therefore it cannot establish a damaging effect for this variant. No variant-specific assay controls, reproducibility data, or quantitative functional result were identified.
PS3: Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.
The target is p.Cys130Arg. The supplied PM5 candidate file contains zero same-residue candidates and no expert-panel or non-expert-majority pathogenic/likely pathogenic comparator; ClinVar for the target is conflicting and cannot establish a different pathogenic missense change at residue 130. A qualifying alternate missense at Cys130 with an established pathogenic classification was not documented, so PM5 cannot be assessed from the available evidence.
Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before. ... Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.
PM6 cannot be assessed because the available case evidence does not report an assumed de novo occurrence, a proband disease phenotype, or parental testing showing that the variant is absent from the parents. No family or reproductive history supports this criterion.
Assumed de novo, but without confirmation of paternity and maternity.
PP1 cannot be assessed because no affected family members, informative meioses, genotype-phenotype cosegregation, or family pedigree is documented for this variant. The available evidence also does not establish the disease context needed to evaluate whether APOE is definitively known to cause that disease.
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease.
The available case evidence does not provide a patient phenotype or family history for this variant that can be evaluated for high specificity to a disease with a single genetic etiology. The APOE literature reviewed describes general APOE epsilon4 risk or unrelated cohorts and does not establish a highly specific phenotype for APOE p.Cys130Arg.
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
BS1 is not assessed rather than applied from the generic 1% default. The variant is common across gnomAD overall (AF 0.142529 in v2.1 and 0.148520 in v4.1), but APOE-associated Alzheimer disease risk is late-onset and incompletely penetrant; a source reviewed for this case states that the APOE epsilon-4 allele is neither necessary nor sufficient to cause Alzheimer disease. A valid BS1 conclusion therefore requires a disorder-specific maximum credible allele frequency using prevalence, penetrance, allelic heterogeneity, and the relevant disease definition. Those inputs and a formal maximum-credible-frequency calculation are not supplied, so the generic 1% threshold alone is insufficient.
Allele frequency is greater than expected for the disorder.
BS2 is not assessed. gnomAD documents many homozygotes, including 2,091 in v2.1 and 17,710 in v4.1, but these aggregate population datasets do not establish that the individuals were healthy adults, their ages, their clinical phenotypes, or that full penetrance was expected at an early age for the relevant disorder. Homozygote counts alone therefore cannot satisfy the BS2 healthy-adult requirement.
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.
BS3 cannot be assessed because no validated in vitro or in vivo functional study in the reviewed evidence directly tests APOE NM_000041.4:c.388T>C (p.Cys130Arg) and demonstrates no damaging effect on protein function or splicing. The APOE4 transgenic-mouse study (PMID:23060451) compares common APOE isoforms rather than this variant and therefore does not provide variant-specific benign functional evidence. No assay controls, quantitative normal-function result, or reproducibility data specific to p.Cys130Arg were identified.
BS3: Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
BS4 cannot be assessed because the available case evidence does not identify affected family members who were tested, non-carriers who should carry the variant, or any documented lack of segregation. There is no family phenotype and genotype information from which to evaluate phenocopy or multiple-variant explanations.
Lack of segregation in affected members of a family.
BP2 requires observation of the evaluated variant in trans with a pathogenic variant for a fully penetrant dominant disorder or in cis with a pathogenic variant in any inheritance pattern. ClinVar contains a multi-variant record named NM_000041.3(APOE):c.[305C>G;388T>C], but its sole submission is an association without assertion criteria and does not establish c.305C>G as pathogenic or provide patient-level phase evidence. No other evidence establishes a pathogenic variant in cis or trans with APOE c.388T>C; BP2 therefore cannot be assessed.
BP2: 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 evidence in the case materials identifies a patient carrying APOE c.388T>C with an alternate molecular basis for the disease. The general APOE and unrelated pharmacogenetic publications reviewed do not establish such a 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_000041.4:c.388T>C in APOE is a missense substitution predicted to produce NP_000032.1:p.(Cys130Arg). 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 APOE, 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
PM3 is limited to recessive disorders and requires the evaluated variant to be detected in trans with a pathogenic variant, with phase established by parental or offspring testing. The case presents APOE c.388T>C (p.Cys130Arg) in an APOE risk-allele/common-variant context and provides no recessive disease model or affected-proband phase data; therefore PM3 is not applicable.
PM3: For recessive disorders, detected in trans with a pathogenic variant ... Note: This requires testing of parents (or offspring) to determine phase.
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_000041.4:c.388T>C in APOE is a missense substitution predicted to produce NP_000032.1:p.(Cys130Arg). 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 APOE, 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
BP3 (Richards et al. 2015, PMID:25741868) applies to in-frame insertions/deletions located in a repetitive region without a known function. NM_000041.4:c.388T>C in APOE is a missense substitution predicted to produce NP_000032.1:p.(Cys130Arg). 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 APOE, 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_000041.4:c.388T>C in APOE is a missense substitution predicted to produce NP_000032.1:p.(Cys130Arg). 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 APOE, 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 APOE, mapped onto the exon structure of NM_000041.4. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| African/African American16245 / 73,686 | 0.221772 hom |
| European (Finnish)11533 / 60,090 | 0.191100 hom |
| European (non-Finnish)174295 / 1,157,104 | 0.1512991 hom |
| Remaining individuals8414 / 60,776 | 0.14623 hom |
| Amish124 / 910 | 0.147 hom |
| Ashkenazi Jewish3458 / 28,748 | 0.12197 hom |
| Admixed American5611 / 52,482 | 0.11299 hom |
| South Asian8686 / 86,316 | 0.1522 hom |
| East Asian4094 / 41,846 | 0.098183 hom |
| Middle Eastern404 / 5,934 | 0.06816 hom |
| African/African American3871 / 17,744 | 0.22403 hom |
| European (Finnish)4073 / 19,798 | 0.21418 hom |
| European (non-Finnish)12460 / 83,842 | 0.15838 hom |
| Remaining individuals785 / 5,748 | 0.1444 hom |
| Ashkenazi Jewish1014 / 8,846 | 0.1151 hom |
| Admixed American2759 / 26,718 | 0.1141 hom |
| South Asian2474 / 24,650 | 0.1149 hom |
| East Asian1201 / 13,574 | 0.08847 hom |
This variant is present in gnomAD v4.1 (AF= 0.14852; MAF= 14.85204%, 232864/1567892 alleles, homozygotes = 17710) and has highest observed frequency in the African/African American population (AF= 0.220463; MAF= 22.04625%, 16245/73686 alleles, homozygotes = 1772); grpmax FAF= 0.217625.
This variant is present in gnomAD v2.1 (AF= 0.142529; MAF= 14.25294%, 28637/200920 alleles, homozygotes = 2091) and has highest observed frequency in the African/African American population (AF= 0.218158; MAF= 21.81583%, 3871/17744 alleles, homozygotes = 403); grpmax FAF= 0.215746.
This variant is present in gnomAD-Canada v1.0 (AF= 0.12580154331050972, 2315/18402 alleles, homozygotes = 168).
NM_000041.4:c.388T>C is a missense variant, NP_000032.1:p.(Cys130Arg), so the governing generic path is REVEL only; SpliceAI is not used for PP3/BP4 in this missense situation. The REVEL score is 0.229, which meets the generic BP4 supporting threshold of <= 0.29. This is a single applicable predictor path, without double-counting SpliceAI or using the uncalibrated BayesDel score.
Missense variant -> REVEL only. Its SpliceAI score says nothing about whether the amino-acid substitution is tolerated, so 'no predicted splice impact' is never BP4 support for a missense variant. ... BP4 (supporting): <= 0.29 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
NM_000041.4:c.388T>C is a missense variant, NP_000032.1:p.(Cys130Arg), so the governing generic path is REVEL only; SpliceAI is not used for PP3/BP4 in this missense situation. The REVEL score is 0.229, below the generic PP3 supporting threshold of >= 0.644. BayesDel is not used because no generic ACMG-strength calibration is established.
Missense variant -> REVEL only. Its SpliceAI score says nothing about whether the amino-acid substitution is tolerated, so 'no predicted splice impact' is never BP4 support for a missense variant. ... 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_000041.4:c.388T>C in APOE is a missense substitution predicted to produce NP_000032.1:p.(Cys130Arg). 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 APOE, 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). REVEL score = 0.229. BayesDel score = -0.312622.
10 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
In E4FAD mice, total apoE levels were lower and total Aβ levels higher than in E2FAD and E3FAD mice.
Abstract; Results sections titled ‘Plaque Deposition Is Greatest in E4FAD’ and ‘Total apoE Levels Are Lower and Total Aβ42 Levels Are Higher in E4FAD Mice’
A systematic literature search was performed for VKORC1 and CYP2C9 and their association with warfarin therapy.
Abstract, Methods
A total of 87 adult patients presenting with mild or moderate TBI to a shock trauma center were enrolled prospectively.
Abstract
The data from these two codons were combined to generate the six APOE genotypes.
Methods, Assessment of exposures and outcome, APOE genotype
In addition to the mutations mentioned previously that can cause AD with high penetrance, a common variant of the apolipoprotein E gene (APOE) known as the ε4-allele has been clearly established as a risk factor for early and late-onset AD (AD2). As the APOE ε4-allele is neither necessary nor sufficient to cause AD, there is a wide consensus that at present there is no clear benefit in APOE genotyping to assist with diagnosis [22] or pre-symptomatic risk assessment.
Inherited dementias, Alzheimer’s disease section; Table 3, Genetics of hereditary dementias
The purpose of this article is to assist in the interpretation and use of CYP2C9 and VKORC1 genotype data for estimating therapeutic warfarin dose to achieve an INR of 2–3, should genotype results be available to the clinician.
Abstract/introduction, page 625
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= 0.14852; MAF= 14.85204%, 232864/1567892 alleles, homozygotes = 17710) and has highest observed frequency in the African/African American population (AF= 0.220463; MAF= 22.04625%, 16245/73686 alleles, homozygotes = 1772); grpmax FAF= 0.217625.
This variant is present in gnomAD v2.1 (AF= 0.142529; MAF= 14.25294%, 28637/200920 alleles, homozygotes = 2091) and has highest observed frequency in the African/African American population (AF= 0.218158; MAF= 21.81583%, 3871/17744 alleles, homozygotes = 403); grpmax FAF= 0.215746.
This variant is present in gnomAD-Canada v1.0 (AF= 0.12580154331050972, 2315/18402 alleles, homozygotes = 168).
This variant has been reported in ClinVar as Uncertain significance (5 clinical laboratories) and as risk factor (2 clinical laboratories) and as Likely pathogenic (2 clinical laboratories) and as Pathogenic (2 clinical laboratories) and as Established risk allele (1 clinical laboratory) and as other (1 clinical laboratory) and as Benign (1 clinical laboratory) and as Likely benign (1 clinical laboratory) and as Likely risk allele (1 clinical laboratory). (ClinVarID = 17864)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.229. BayesDel score = -0.312622.
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV52985231, n = 14 times).
This variant does not lie in a statistically significant hotspot.