ClinVar

Description

Variant summary: ABCB11 c.2783G>A (p.Arg928Gln) results in a conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 248692 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2783G>A has been reported in the literature in at least one individual affected with intrahepatic cholestasis without strong evidence for causality (e.g., Liu_2013, Li_2015). These reports do not provide unequivocal conclusions about association of the variant with Familial Intrahepatic Cholestasis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) have cited the variant, and both laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.