ClinVar Miner

Submissions for variant NM_003742.4(ABCB11):c.3676C>T (p.Arg1226Cys)

gnomAD frequency: 0.00002  dbSNP: rs772241929
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000734213 SCV000862337 uncertain significance not provided 2018-07-09 criteria provided, single submitter clinical testing
Rolfs Rare Disease Consulting, Rolfs Consulting Und Verwaltungs GmbH RCV003485639 SCV004232518 likely pathogenic Progressive familial intrahepatic cholestasis type 2 2021-01-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV004569420 SCV005059074 likely pathogenic Benign recurrent intrahepatic cholestasis type 2 2024-03-30 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV003485639 SCV005907421 uncertain significance Progressive familial intrahepatic cholestasis type 2 2025-01-22 criteria provided, single submitter curation The p.Arg1226Cys variant in ABCB11 has been reported in 2 individuals with BSEP deficiency (PMID: 35894240, vanWessel et al. 2020), and has been identified in 0.01% (7/59980) of Admixed American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs772241929). Although this variant has been seen in the general population in a heterozygous state, its frequency is not high enough to rule out a pathogenic role. This variant has also been reported in ClinVar (Variation ID: 597949) and has been interpreted as likely pathogenic by Rolfs Rare Disease Consulting (Rolfs Consulting Und Verwaltungs GmbH) and Baylor Genetics, and as a variant of uncertain significance by Eurofins Ntd Llc (ga). Of the two affected individuals, one of those was a homozygote, which increases the likelihood that the p.Arg1226Cys variant is pathogenic (vanWessel et al. 2020). In summary, the clinical significance of the p.Arg1226Cys variant is uncertain. ACMG/AMP Criteria applied: PP3_moderate, PM2_supporting, PM3_supporting (Richards 2015).

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