chr12-20883477-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019844.4(SLCO1B3):c.1557A>G(p.Ala519Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 1,594,240 control chromosomes in the GnomAD database, including 556,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 42474 hom., cov: 32)

Exomes 𝑓: 0.84 ( 513860 hom. )

Consequence

SLCO1B3
NM_019844.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.70

Variant links:

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]

SLCO1B3 links:

SLCO1B3-SLCO1B7 (HGNC:54403): (SLCO1B3-SLCO1B7 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring SLCO1B3 (solute carrier organic anion transporter family member 1B3) and SLCO1B7 (solute carrier organic anion transporter family member 1B7 (putative)) genes on chromosome 12. The readthrough transcript encodes a protein that shares sequence identity with both the upstream and downstream genes. [provided by RefSeq, Jun 2019]

SLCO1B3-SLCO1B7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 12-20883477-A-G is Benign according to our data. Variant chr12-20883477-A-G is described in ClinVar as [Benign]. Clinvar id is 261183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-20883477-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B3	NM_019844.4 link	c.1557A>G	p.Ala519Ala	synonymous_variant	Exon 13 of 16	ENST00000381545.8	NP_062818.1	Q9NPD5-1B3KP78
SLCO1B3-SLCO1B7	NM_001371097.1 link	c.1557A>G	p.Ala519Ala	synonymous_variant	Exon 11 of 16		NP_001358026.1
SLCO1B3	NM_001349920.2 link	c.1473A>G	p.Ala491Ala	synonymous_variant	Exon 11 of 14		NP_001336849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8 link	c.1557A>G	p.Ala519Ala	synonymous_variant	Exon 13 of 16	2	NM_019844.4	ENSP00000370956.4		Q9NPD5-1
SLCO1B3-SLCO1B7	ENST00000540229.1 link	c.1557A>G	p.Ala519Ala	synonymous_variant	Exon 11 of 16	2		ENSP00000441269.1		A0A0A6YYJ9

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110100

AN:

151922

Hom.:

42477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.855

Gnomad AMR

AF:

0.811

Gnomad ASJ

AF:

0.890

Gnomad EAS

AF:

0.719

Gnomad SAS

AF:

0.900

Gnomad FIN

AF:

0.746

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.853

Gnomad OTH

AF:

0.778

GnomAD3 exomes

AF:

0.811

AC:

193111

AN:

238070

Hom.:

79892

AF XY:

0.826

AC XY:

106812

AN XY:

129274

show subpopulations

Gnomad AFR exome

AF:

0.428

Gnomad AMR exome

AF:

0.806

Gnomad ASJ exome

AF:

0.894

Gnomad EAS exome

AF:

0.729

Gnomad SAS exome

AF:

0.908

Gnomad FIN exome

AF:

0.755

Gnomad NFE exome

AF:

0.855

Gnomad OTH exome

AF:

0.829

GnomAD4 exome

AF:

0.840

AC:

1212001

AN:

1442200

Hom.:

513860

Cov.:

AF XY:

0.844

AC XY:

606036

AN XY:

718018

show subpopulations

Gnomad4 AFR exome

AF:

0.418

Gnomad4 AMR exome

AF:

0.805

Gnomad4 ASJ exome

AF:

0.894

Gnomad4 EAS exome

AF:

0.710

Gnomad4 SAS exome

AF:

0.909

Gnomad4 FIN exome

AF:

0.762

Gnomad4 NFE exome

AF:

0.857

Gnomad4 OTH exome

AF:

0.825

GnomAD4 genome

AF:

0.724

AC:

110124

AN:

152040

Hom.:

42474

Cov.:

AF XY:

0.723

AC XY:

53751

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.436

Gnomad4 AMR

AF:

0.811

Gnomad4 ASJ

AF:

0.890

Gnomad4 EAS

AF:

0.719

Gnomad4 SAS

AF:

0.902

Gnomad4 FIN

AF:

0.746

Gnomad4 NFE

AF:

0.853

Gnomad4 OTH

AF:

0.778

Alfa

AF:

0.796

Hom.:

26613

Bravo

AF:

0.717

Asia WGS

AF:

0.763

AC:

2652

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Rotor syndrome

Benign:3

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: 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 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. -

Nov 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.28

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over