ClinVar Miner

Submissions for variant NM_001206979.2(NR1H4):c.526C>T (p.Arg176Ter)

dbSNP: rs113090017
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV000240831 SCV000258400 pathogenic Progressive familial intrahepatic cholestasis type 1 2015-12-17 criteria provided, single submitter clinical testing This variant was found in homozygous status in two affected members from a Hispanic family.
Labcorp Genetics (formerly Invitae), Labcorp RCV002515513 SCV003441116 pathogenic not provided 2022-08-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg176*) in the NR1H4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NR1H4 are known to be pathogenic (PMID: 11030617, 26888176). This variant is present in population databases (rs113090017, gnomAD 0.02%). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 219164). This premature translational stop signal has been observed in individual(s) with progressive familial intrahepatic cholestasis (PMID: 26888176).
OMIM RCV000239570 SCV000297936 pathogenic Cholestasis, progressive familial intrahepatic, 5 2012-02-01 no assertion criteria provided literature only
PreventionGenetics, part of Exact Sciences RCV004754356 SCV005348001 pathogenic NR1H4-related disorder 2024-05-23 no assertion criteria provided clinical testing The NR1H4 c.526C>T variant is predicted to result in premature protein termination (p.Arg176*). This variant has been reported in the homozygous state in two siblings with progressive familial intrahepatic cholestasis (Gomez-Ospina et al. 2016. PubMed ID: 26888176) This variant has also been reported in the homozygous state in an unrelated individual with progressive familial intrahepatic cholestasis and in the heterozygous state in an individual with idiopathic infantile cholestasis in whom a second potentially pathogenic variant was not identified (Himes et al. 2020. PubMed ID: 32443034; Chen et al. 2012. PubMed ID: 21633855). Nonsense variants in NR1H4 are expected to be pathogenic. This variant is interpreted as pathogenic.

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