ClinVar Miner

Submissions for variant NM_000443.4(ABCB4):c.475C>T (p.Arg159Ter)

gnomAD frequency: 0.00001  dbSNP: rs377160065
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000732592 SCV000860566 pathogenic not provided 2018-04-10 criteria provided, single submitter clinical testing
Mendelics RCV000987917 SCV001137410 pathogenic Progressive familial intrahepatic cholestasis type 1 2019-05-28 criteria provided, single submitter clinical testing
Genetics and Molecular Pathology, SA Pathology RCV003447558 SCV004175670 pathogenic Low phospholipid associated cholelithiasis 2021-11-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000732592 SCV004294484 pathogenic not provided 2024-06-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg159*) in the ABCB4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCB4 are known to be pathogenic (PMID: 17726488, 25755532). This variant is present in population databases (rs377160065, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with progressive familial intrahepatic cholestasis type 3 and low-phospholipid-associated cholelithiasis (PMID: 17726488, 23533021, 34961929). ClinVar contains an entry for this variant (Variation ID: 596680). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005046999 SCV005674294 pathogenic Progressive familial intrahepatic cholestasis type 3; Low phospholipid associated cholelithiasis; Cholestasis, intrahepatic, of pregnancy, 3 2024-03-07 criteria provided, single submitter clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV001003563 SCV001161924 likely pathogenic Cholestasis, intrahepatic, of pregnancy, 3 no assertion criteria provided research
PreventionGenetics, part of Exact Sciences RCV004535856 SCV004710272 pathogenic ABCB4-related disorder 2024-02-10 no assertion criteria provided clinical testing The ABCB4 c.475C>T variant is predicted to result in premature protein termination (p.Arg159*). This variant was reported in the homozygous state to be causative for autosomal recessive progressive familial intrahepatic cholestasis (Table S4, Hertel et al. 2021. PubMed ID: 34016879; Bakır et al. 2021. PubMed ID: 34961929). This variant was also reported in the heterozygous state, in the absence of a second pathogenic variant, in association with autosomal recessive progressive familial intrahepatic cholestasis and low-phospholipid-associated cholelithiasis syndrome (Degiorgio et al. 2007. PubMed ID: 17726488; Poupon et al. 2013. PubMed ID: 23533021; Sharma et al. 2018. PubMed ID: 29973134). This variant is reported in 0.0050% of alleles in individuals of East Asian descent in gnomAD. Nonsense variants in ABCB4 are expected to be pathogenic. This variant is interpreted as pathogenic.

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