ClinVar Miner

Submissions for variant NM_003742.4(ABCB11):c.3512T>C (p.Met1171Thr)

gnomAD frequency: 0.00071  dbSNP: rs183621659
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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) RCV000400668 SCV000337456 uncertain significance not provided 2017-10-02 criteria provided, single submitter clinical testing
Invitae RCV000400668 SCV001023879 likely benign not provided 2024-01-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001133700 SCV001293410 uncertain significance Progressive familial intrahepatic cholestasis type 2 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Mayo Clinic Laboratories, Mayo Clinic RCV000400668 SCV002541892 uncertain significance not provided 2021-09-14 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003920081 SCV004730784 likely benign ABCB11-related disorder 2022-02-09 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Natera, Inc. RCV001133700 SCV001458319 uncertain significance Progressive familial intrahepatic cholestasis type 2 2019-10-28 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000400668 SCV001554104 uncertain significance not provided no assertion criteria provided clinical testing The ABCB11 p.Met1171Thr variant was not identified in the literature nor was it identified in LOVD 3.0. The variant was identified in dbSNP (ID: rs183621659) and ClinVar (classified as uncertain significance by EGL Genetic Diagnostics and likely benign by Invitae). The variant was identified in control databases in 57 of 280648 chromosomes at a frequency of 0.0002031 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: African in 55 of 24192 chromosomes (freq: 0.002273), Other in 1 of 7140 chromosomes (freq: 0.00014), Latino in 1 of 35376 chromosomes (freq: 0.000028), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), or South Asian populations. The p.Met1171Thr residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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