rs61736830
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_019844.4(SLCO1B3):c.759T>A(p.Arg253=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,612,334 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0081 ( 13 hom., cov: 32)
Exomes 𝑓: 0.00082 ( 13 hom. )
Consequence
SLCO1B3
NM_019844.4 synonymous
NM_019844.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.47
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
Variant 12-20875266-T-A is Benign according to our data. Variant chr12-20875266-T-A is described in ClinVar as [Benign]. Clinvar id is 307895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.47 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0081 (1233/152252) while in subpopulation AFR AF= 0.0277 (1151/41546). AF 95% confidence interval is 0.0264. There are 13 homozygotes in gnomad4. There are 605 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 13 Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLCO1B3 | NM_019844.4 | c.759T>A | p.Arg253= | synonymous_variant | 9/16 | ENST00000381545.8 | |
SLCO1B3-SLCO1B7 | NM_001371097.1 | c.759T>A | p.Arg253= | synonymous_variant | 7/16 | ||
SLCO1B3 | NM_001349920.2 | c.675T>A | p.Arg225= | synonymous_variant | 7/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLCO1B3 | ENST00000381545.8 | c.759T>A | p.Arg253= | synonymous_variant | 9/16 | 2 | NM_019844.4 | P1 | |
SLCO1B3 | ENST00000261196.6 | c.759T>A | p.Arg253= | synonymous_variant | 7/14 | 1 | P1 | ||
SLCO1B3 | ENST00000540853.5 | c.759T>A | p.Arg253= | synonymous_variant | 8/8 | 1 | |||
SLCO1B3 | ENST00000544370.1 | c.231T>A | p.Arg77= | synonymous_variant | 3/10 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00808 AC: 1229AN: 152134Hom.: 13 Cov.: 32
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GnomAD3 exomes AF: 0.00207 AC: 516AN: 249860Hom.: 12 AF XY: 0.00171 AC XY: 231AN XY: 135132
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GnomAD4 exome AF: 0.000815 AC: 1190AN: 1460082Hom.: 13 Cov.: 32 AF XY: 0.000708 AC XY: 514AN XY: 726402
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GnomAD4 genome ? AF: 0.00810 AC: 1233AN: 152252Hom.: 13 Cov.: 32 AF XY: 0.00813 AC XY: 605AN XY: 74454
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Rotor syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 10, 2023 | - - |
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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Name
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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