rs3764006

Positions:

• chr12-20901435-G-A
• chr12-20901435-G-C
• chr12-20901435-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_019844.4(SLCO1B3):​c.1833G>A​(p.Gly611Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 1,561,636 control chromosomes in the GnomAD database, including 582,197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (42957 hom., cov: 32)
  • Exomes 𝑓: 0.87 (539240 hom.)
• Consequence: SLCO1B3 NM_019844.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.38

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: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]

LOC124902894 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-20901435-G-A is Benign according to our data. Variant chr12-20901435-G-A is described in ClinVar as [Benign]. Clinvar id is 440286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-20901435-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.1833G>A	p.Gly611Gly	synonymous_variant	15/16	ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.1833G>A	p.Gly611Gly	synonymous_variant	13/16		NP_001358026.1
SLCO1B3	NM_001349920.2	c.1749G>A	p.Gly583Gly	synonymous_variant	13/14		NP_001336849.1
LOC124902894	XM_047429949.1	c.-90G>A		5_prime_UTR_variant	1/10		XP_047285905.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.1833G>A	p.Gly611Gly	synonymous_variant	15/16	2	NM_019844.4	ENSP00000370956.4
SLCO1B3-SLCO1B7	ENST00000540229.1	c.1833G>A	p.Gly611Gly	synonymous_variant	13/16	2		ENSP00000441269.1

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108446 AN: 151900 Hom.: 42953 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.760

GnomAD3 exomes AF: 0.817 AC: 171302 AN: 209728 Hom.: 72283 AF XY: 0.836 AC XY: 95699 AN XY: 114476

Gnomad AFR exome AF: 0.319

Gnomad AMR exome AF: 0.765

Gnomad ASJ exome AF: 0.893

Gnomad EAS exome AF: 0.742

Gnomad SAS exome AF: 0.935

Gnomad FIN exome AF: 0.776

Gnomad NFE exome AF: 0.885

Gnomad OTH exome AF: 0.837

GnomAD4 exome AF: 0.870 AC: 1225839 AN: 1409618 Hom.: 539240 Cov.: 28 AF XY: 0.873 AC XY: 611656 AN XY: 700460

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.761

Gnomad4 ASJ exome AF: 0.898

Gnomad4 EAS exome AF: 0.771

Gnomad4 SAS exome AF: 0.936

Gnomad4 FIN exome AF: 0.784

Gnomad4 NFE exome AF: 0.892

Gnomad4 OTH exome AF: 0.848

GnomAD4 genome AF: 0.714 AC: 108481 AN: 152018 Hom.: 42957 Cov.: 32 AF XY: 0.712 AC XY: 52881 AN XY: 74322

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.895

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.938

Gnomad4 FIN AF: 0.769

Gnomad4 NFE AF: 0.887

Gnomad4 OTH AF: 0.763

Alfa AF: 0.860 Hom.: 129270

Bravo AF: 0.697

Asia WGS AF: 0.797 AC: 2770 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Rotor syndrome Benign:2

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	Genome-Nilou Lab	Jul 15, 2021	- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.65
DANN	Benign	0.86

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: rs3764006; hg19: chr12-21054369; COSMIC: COSV53947607;