ClinVar

Description

Variant summary: ABCG8 c.628G>A (p.Val210Met) results in a conservative amino acid change located in the ABC transporter-like, ATP-binding domain (IPR003439) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0036 in 250926 control chromosomes, predominantly at a frequency of 0.048 within the African or African-American subpopulation in the gnomAD database, including 17 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 10-fold of the estimated maximal expected allele frequency for a pathogenic variant in ABCG8 causing Early Onset Coronary Artery Disease phenotype (0.005), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.628G>A has been reported in the literature in individual(s) affected with Early Onset Coronary Artery Disease as an Likely Benign change (Reeskamp_2020). These report(s) do not provide unequivocal conclusions about association of the variant with Early Onset Coronary Artery Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 32088153). ClinVar contains an entry for this variant (Variation ID: 336070). Based on the evidence outlined above, the variant was classified as likely benign.