ClinVar Miner

Submissions for variant NM_018849.3(ABCB4):c.140G>A (p.Arg47Gln) (rs372685632)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724891 SCV000230097 uncertain significance not provided 2018-03-15 criteria provided, single submitter clinical testing
GeneDx RCV000724891 SCV000617822 uncertain significance not provided 2017-06-28 criteria provided, single submitter clinical testing The R47Q variant has been reported previously in patients with PFIC3, LPAC, and IPC who also harbored another ABCB4 gene variant (Davit-Spraul et al., 2010; Poupon et al., 2013; Frider et al., 2015). Expression studies revealed that R47Q is associated with reduced protein levels compared to wild-type, however R47Q was not associated with altered protein localization (Frider et al., 2015). The R47Q variant is observed in 2/11396 (0.02%) alleles from individuals of Latino background, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R47Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000391687 SCV000470170 uncertain significance Cholecystitis 2017-04-27 criteria provided, single submitter clinical testing The ABCB4 c.140G>A (p.Arg47Gln) variant is a missense variant that has been reported in at least two studies, where it was found in a compound heterozygous state in two individuals with low-phospholipid associated cholestasis syndrome (Wendum et al. 2012; Poupon et al. 2013). Control data are unavailable for this variant, which is reported at a frequency of 0.00009 in the European (non-Finnish) population of the Exome Aggregation Consortium. The evidence for this variant is limited. The p.Arg47Gln variant is thus classified as a variant of unknown significance but suspicious for pathogenicity for ABCB4-related intrahepatic cholestasis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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