rs2053098

chr12-20883477-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_019844.4(SLCO1B3):c.1557A>G(p.Ala519=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.70

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-SLCO1B7 (HGNC:):

ACMG classification

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/exons	MANE	UniProt
SLCO1B3	NM_019844.4	c.1557A>G	p.Ala519=	synonymous_variant	13/16	ENST00000381545.8
SLCO1B3-SLCO1B7	NM_001371097.1	c.1557A>G	p.Ala519=	synonymous_variant	11/16
SLCO1B3	NM_001349920.2	c.1473A>G	p.Ala491=	synonymous_variant	11/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.1557A>G	p.Ala519=	synonymous_variant	13/16	2	NM_019844.4	P1
SLCO1B3	ENST00000261196.6	c.1557A>G	p.Ala519=	synonymous_variant	11/14	1		P1
SLCO1B3	ENST00000544370.1	c.1029A>G	p.Ala343=	synonymous_variant	7/10	5

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110100 AN: 151922 Hom.: 42477 Cov.: 32

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

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.: 32 AF XY: 0.844 AC XY: 606036 AN XY: 718018

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.: 32 AF XY: 0.723 AC XY: 53751 AN XY: 74308

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Rotor syndrome Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

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

Other links and lift over

dbSNP: rs2053098; hg19: chr12-21036411; COSMIC: COSV53938181;