ClinVar

Description

Across a selection of the available literature, the ABCB4 c.959C>T (p.Ser320Phe) missense variant has been identified in a homozygous state in four patients with intrahepatic cholestasis of pregnancy, in a homozygous state in one patient with progressive familial intrahepatic cholestasis type 3, in a homozygous state in one patient with low phospholipid associated cholelithiasis, and in a compound heterozygotes state in seven patients with progressive familial intrahepatic cholestasis type 3 (Rosmorduc et al. 2001; Rosmorduc et al. 2003; Pauli-Magnus et al. 2004; Keitel et al. 2006; Degiorgio et al. 2007; Colombo et al. 2011; Oliveira et al. 2016). The p.Ser320Phe variant was absent from 630 controls and is reported at a frequency of 0.00020 in the European (non-Finnish) population of the Exome Aggregation Consortium. Transfection of the p.Ser320Phe variant into HEK293T and MDCK-II cells showed that the variant protein had similar activity as compared to wild type, however the expression levels were slightly reduced (Kim et al. 2013; Andress et al. 2014; Gordo-Gilart et al. 2016). Based on the evidence, the p.Ser320Phe variant is classified as pathogenic for ABCB4-related intrahepatic cholestasis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.