ClinVar Miner

Submissions for variant NM_000443.4(ABCB4):c.808G>A (p.Gly270Arg)

dbSNP: rs551234479
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002271737 SCV002555602 likely pathogenic Progressive familial intrahepatic cholestasis 2022-06-03 criteria provided, single submitter clinical testing Variant summary: ABCB4 c.808G>A (p.Gly270Arg) results in a non-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 damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251248 control chromosomes. c.808G>A has been reported in the literature in at-least two homozygous individuals affected with Progressive Familial Intrahepatic Cholestasis Type 3 (example, Shagrani_2017). These data indicate that the variant is likely to be associated with disease. 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 pathogenic.
GeneDx RCV002511147 SCV002820413 uncertain significance not provided 2022-12-28 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28039895)
PreventionGenetics, part of Exact Sciences RCV004534026 SCV004743826 uncertain significance ABCB4-related disorder 2023-12-01 criteria provided, single submitter clinical testing The ABCB4 c.808G>A variant is predicted to result in the amino acid substitution p.Gly270Arg. This variant in the homozygous condition was reported in two individuals with progressive familial intrahepatic cholestasis (Table 1, Shagrani et al. 2017. PubMed ID: 28039895). This variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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