ClinVar Miner

Submissions for variant NM_000443.4(ABCB4):c.1313C>T (p.Thr438Met)

gnomAD frequency: 0.00019  dbSNP: rs142271471
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000596236 SCV000707406 uncertain significance not provided 2017-03-29 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002265817 SCV002548021 uncertain significance not specified 2022-05-03 criteria provided, single submitter clinical testing Variant summary: ABCB4 c.1313C>T (p.Thr438Met) results in a non-conservative amino acid change located in the ABC transporter-like, ATP-binding domain (IPR003439) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 9.2e-05 in 251322 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in ABCB4 causing Familial Intrahepatic Cholestasis (9.2e-05 vs 0.0022), allowing no conclusion about variant significance. c.1313C>T has been reported in the literature as a VUS (class 3 variant) in a cohort of individuals with ABCB4 deficiency (example, de Vries_2020). These report(s) do not provide unequivocal conclusions about association of the variant with Familial Intrahepatic Cholestasis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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