ClinVar Miner

Submissions for variant NM_003742.4(ABCB11):c.1468A>G (p.Asn490Asp)

gnomAD frequency: 0.00004  dbSNP: rs553076953
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001130296 SCV001289870 uncertain significance Progressive familial intrahepatic cholestasis type 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001844267 SCV002103710 uncertain significance not specified 2022-02-15 criteria provided, single submitter clinical testing Variant summary: ABCB11 c.1468A>G (p.Asn490Asp) results in a conservative amino acid change located in the ABC transporter-like, ATP-binding domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 247966 control chromosomes. c.1468A>G has been reported in the literature in an individual affected with severe intrahepatic cholestasis, without second mutation reported, however other genes were not tested in this patient (Strautnieks_2008). This report does not provide unequivocal conclusions about association of the variant with Familial Intrahepatic Cholestasis. Functional studies have shown the mutation to result in significantly reduced levels of mature protein as well as significantly reduced taurocholate transport activity compared with wild-type (Byrne_2009). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002482255 SCV002776707 uncertain significance Benign recurrent intrahepatic cholestasis type 2; Progressive familial intrahepatic cholestasis type 2 2022-03-11 criteria provided, single submitter clinical testing

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