ClinVar Miner

Submissions for variant NM_000040.3(APOC3):c.179+1G>T (rs140621530)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000780860 SCV000918479 likely benign not specified 2018-09-04 criteria provided, single submitter clinical testing Variant summary: APOC3 c.179+1G>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: three predict the variant abolishes, while one predicts the variant weakens a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 5.8e-05 in 273618 control chromosomes, predominantly within the African subpopulation at a frequency of 0.00059 in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 30 fold of the estimated maximal expected allele frequency for a pathogenic variant in APOC3 causing Early Onset Coronary Artery Disease phenotype (2e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. The variant has been reported in literature suggesting the variant has a protective effect (Crosby 2014). 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.
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000128451 SCV000172133 protective Coronary heart disease 2014-06-18 no assertion criteria provided literature only
OMIM RCV000148018 SCV000195518 pathogenic Hyperalphalipoproteinemia 2 2014-06-18 no assertion criteria provided literature only

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