ClinVar Miner

Submissions for variant NM_000443.4(ABCB4):c.2869C>T (p.Arg957Ter)

gnomAD frequency: 0.00002  dbSNP: rs121918440
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000778841 SCV000915234 likely pathogenic Low phospholipid associated cholelithiasis 2018-12-13 criteria provided, single submitter clinical testing The ABCB4 c.2869C>T (p.Arg957Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The p.Arg957Ter variant has been reported in two studies and is found in two probands with progressive familial intrahepatic cholestasis, including one in a homozygous state and one in a compound heterozygous state (de Vree et al. 1998; Stalke et al. 2017). Canalicular staining for ABCB4 protein was negative in liver tissue of the homozygous proband, and Northern blot and Western blot analysis showed low level or absence of RNA and protein (de Vree et al. 1998). The homozygous proband was from a consanguineous family and no other probands with liver disease were reported in this family, except for the mother who had experienced episodes of cholestasis during pregnancy (de Vree et al. 1998). Control data are unavailable for this variant and it is not found in the 1000 Genomes Project, the Exome Sequencing Project, the Exome Aggregation Consortium, or the Genome Aggregation Database. Based on the evidence and potential impact of stop-gained variants, this variant is classified as likely pathogenic for ABCB4-related intrahepatic cholestasis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Revvity Omics, Revvity Omics RCV001781265 SCV002020442 pathogenic not provided 2020-02-03 criteria provided, single submitter clinical testing
Invitae RCV001781265 SCV004294476 pathogenic not provided 2023-06-25 criteria provided, single submitter clinical testing 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: 13687). This premature translational stop signal has been observed in individual(s) with familial intrahepatic cholestasis (PMID: 9419367). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg957*) 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).
OMIM RCV000014683 SCV000034938 pathogenic Progressive familial intrahepatic cholestasis type 3 2017-10-18 no assertion criteria provided literature only
OMIM RCV000033063 SCV000056843 pathogenic Cholestasis, intrahepatic, of pregnancy, 3 2017-10-18 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.