ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.10385A>G (p.Tyr3462Cys)

gnomAD frequency: 0.00014  dbSNP: rs200305144
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001838142 SCV001006986 benign Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 2024-01-17 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192835 SCV001361218 likely benign not specified 2019-04-16 criteria provided, single submitter clinical testing Variant summary: APOB c.10385A>G (p.Tyr3462Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00016 in 253350 control chromosomes, predominantly at a frequency of 0.0035 within the Ashkenazi Jewish subpopulation in the gnomAD database. The observed variant frequency within Ashkenazi Jewish control individuals in the gnomAD database is approximately 112 fold of the estimated maximal expected allele frequency for a pathogenic variant in APOB causing Familial Defective Apolipoprotein B-100 phenotype (3.1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Ashkenazi Jewish origin. c.10385A>G has been reported in the literature in an individual affected with hypertriglyceridemia (Johansen_2010). However, this report does not provide unequivocal conclusions about association of the variant with Familial Defective Apolipoprotein B-100. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign.
Ambry Genetics RCV002388392 SCV002696703 likely benign Cardiovascular phenotype 2021-10-11 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences RCV004540091 SCV004782311 likely benign APOB-related disorder 2020-05-22 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV001192835 SCV004847718 likely benign not specified 2021-11-09 criteria provided, single submitter clinical testing The p.Tyr3462Cys variant in APOB is classified as likely benign because it has been identified in 0.35% (35/10052) of Ashkenazi Jewish chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BS1, BP4.

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