chr12-20883534-T-C
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_019844.4(SLCO1B3):āc.1614T>Cā(p.Val538=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000497 in 1,605,556 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0024 ( 4 hom., cov: 33)
Exomes š: 0.00029 ( 0 hom. )
Consequence
SLCO1B3
NM_019844.4 synonymous
NM_019844.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.630
Genes affected
SLCO1B3 (HGNC:10961): (solute carrier organic anion transporter family member 1B3) This gene encodes a liver-specific member of the organic anion transporter family. The encoded protein is a transmembrane receptor that mediates the sodium-independent uptake of endogenous and xenobiotic compounds and plays a critical role in bile acid and bilirubin transport. Mutations in this gene are a cause of Rotor type hyperbilirubinemia. Alternative splicing of this gene and the use of alternative promoters results in transcript variants encoding different isoforms that differ in their tissue specificity. [provided by RefSeq, Mar 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 12-20883534-T-C is Benign according to our data. Variant chr12-20883534-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 307908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.63 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 4 Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLCO1B3 | NM_019844.4 | c.1614T>C | p.Val538= | synonymous_variant | 13/16 | ENST00000381545.8 | |
SLCO1B3-SLCO1B7 | NM_001371097.1 | c.1614T>C | p.Val538= | synonymous_variant | 11/16 | ||
SLCO1B3 | NM_001349920.2 | c.1530T>C | p.Val510= | synonymous_variant | 11/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLCO1B3 | ENST00000381545.8 | c.1614T>C | p.Val538= | synonymous_variant | 13/16 | 2 | NM_019844.4 | P1 | |
SLCO1B3 | ENST00000261196.6 | c.1614T>C | p.Val538= | synonymous_variant | 11/14 | 1 | P1 | ||
SLCO1B3 | ENST00000544370.1 | c.1086T>C | p.Val362= | synonymous_variant | 7/10 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00244 AC: 372AN: 152196Hom.: 4 Cov.: 33
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GnomAD3 exomes AF: 0.000586 AC: 142AN: 242498Hom.: 1 AF XY: 0.000495 AC XY: 65AN XY: 131324
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GnomAD4 exome AF: 0.000293 AC: 426AN: 1453242Hom.: 0 Cov.: 31 AF XY: 0.000261 AC XY: 189AN XY: 723012
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GnomAD4 genome AF: 0.00244 AC: 372AN: 152314Hom.: 4 Cov.: 33 AF XY: 0.00222 AC XY: 165AN XY: 74482
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Rotor syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jun 15, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
SLCO1B3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 23, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at