ClinVar Miner

Submissions for variant NM_003742.4(ABCB11):c.2343+1G>T

dbSNP: rs774411820
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001039189 SCV001202705 pathogenic not provided 2023-08-02 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 19 of the ABCB11 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ABCB11 are known to be pathogenic (PMID: 18395098, 20232290). This variant is not present in population databases (gnomAD no frequency). 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: 837780). Disruption of this splice site has been observed in individuals with clinical features of progressive familial intrahepatic cholestasis (PMID: 16871584, 24991443).
GeneDx RCV001039189 SCV001812441 likely pathogenic not provided 2020-12-31 criteria provided, single submitter clinical testing Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown; Observed with a pathogenic variant in individuals with progressive familial intrahepatic cholestasis in published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes in some cases (Scheimann et al., 2007; Strautnieks et al., 2008); Observed in the heterozygous state in a female with intrahepatic cholestasis of pregnancy (Dixon et al., 2017); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 26689913, 18395098, 28924228, 17452236, 25525159, 24991443)
PreventionGenetics, part of Exact Sciences RCV003983825 SCV004800026 pathogenic ABCB11-related disorder 2023-11-16 criteria provided, single submitter clinical testing The ABCB11 c.2343+1G>T variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant was reported with a second ABCB11 variant or in the homozygous state in individuals with familial progressive intrahepatic cholestasis (Scheimann et al 2007. PubMed ID: 17452236; Tibesar E et al 2014. PubMed ID: 24991443; Reported as IVS19+2T>C in Knisely AS et al 2006. PubMed ID: 16871584). This variant has not been reported in a large population database (, indicating this variant is rare. Variants that disrupt the consensus splice donor site in ABCB11 are expected to be pathogenic. This variant is interpreted as pathogenic.
Natera, Inc. RCV001274996 SCV001459645 likely pathogenic Progressive familial intrahepatic cholestasis type 2 2020-09-16 no assertion criteria provided clinical testing

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