rs77271279
Positions:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP3BP6BS1BS2
The NM_006446.5(SLCO1B1):c.481+1G>T variant causes a splice donor change. The variant allele was found at a frequency of 0.00162 in 1,547,080 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0086 ( 24 hom., cov: 33)
Exomes 𝑓: 0.00086 ( 22 hom. )
Consequence
SLCO1B1
NM_006446.5 splice_donor
NM_006446.5 splice_donor
Scores
1
3
3
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 4.25
Genes affected
SLCO1B1 (HGNC:10959): (solute carrier organic anion transporter family member 1B1) 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 numerous endogenous compounds including bilirubin, 17-beta-glucuronosyl estradiol and leukotriene C4. This protein is also involved in the removal of drug compounds such as statins, bromosulfophthalein and rifampin from the blood into the hepatocytes. Polymorphisms in the gene encoding this protein are associated with impaired transporter function. [provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PP3
?
Multiple lines of computational evidence support a deleterious effect 5: Cadd, dbscSNV1_ADA, dbscSNV1_RF, max_spliceai, Eigen [when BayesDel_addAF, BayesDel_noAF, MutationTaster was below the threshold]
BP6
?
Variant 12-21176898-G-T is Benign according to our data. Variant chr12-21176898-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 307938.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}. Variant chr12-21176898-G-T is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00862 (1311/152088) while in subpopulation AFR AF= 0.0297 (1233/41518). AF 95% confidence interval is 0.0283. There are 24 homozygotes in gnomad4. There are 608 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1311 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLCO1B1 | NM_006446.5 | c.481+1G>T | splice_donor_variant | ENST00000256958.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLCO1B1 | ENST00000256958.3 | c.481+1G>T | splice_donor_variant | 1 | NM_006446.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00861 AC: 1309AN: 151970Hom.: 23 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00235 AC: 589AN: 250278Hom.: 7 AF XY: 0.00185 AC XY: 250AN XY: 135352
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GnomAD4 exome AF: 0.000858 AC: 1197AN: 1394992Hom.: 22 Cov.: 27 AF XY: 0.000716 AC XY: 499AN XY: 696988
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GnomAD4 genome ? AF: 0.00862 AC: 1311AN: 152088Hom.: 24 Cov.: 33 AF XY: 0.00818 AC XY: 608AN XY: 74362
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Rotor syndrome Pathogenic:1Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 26, 2023 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2012 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D
GERP RS
Splicing
Name
Calibrated prediction
Score
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at