chr12-20901435-G-A

Variant names:

• chr12-20901435-G-A
• rs3764006
• NM_019844.4:c.1833G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 440286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.1833G>A	p.Gly611Gly	synonymous_variant	Exon 15 of 16	ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.1833G>A	p.Gly611Gly	synonymous_variant	Exon 13 of 16		NP_001358026.1
SLCO1B3	NM_001349920.2	c.1749G>A	p.Gly583Gly	synonymous_variant	Exon 13 of 14		NP_001336849.1
LOC124902894	XM_047429949.1	c.-90G>A		5_prime_UTR_variant	Exon 1 of 10		XP_047285905.1

Ensembl

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

GnomAD2 exomes AF: 0.817 AC: 171302 AN: 209728 AF XY: 0.836

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 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

African (AFR) AF: 0.317 AC: 9683 AN: 30584

American (AMR) AF: 0.761 AC: 24513 AN: 32220

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 22030 AN: 24526

East Asian (EAS) AF: 0.771 AC: 29083 AN: 37698

South Asian (SAS) AF: 0.936 AC: 70793 AN: 75656

European-Finnish (FIN) AF: 0.784 AC: 41566 AN: 53008

Middle Eastern (MID) AF: 0.886 AC: 4810 AN: 5426

European-Non Finnish (NFE) AF: 0.892 AC: 973884 AN: 1092180

Other (OTH) AF: 0.848 AC: 49477 AN: 58320

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

African (AFR) AF: 0.341 AC: 14128 AN: 41400

American (AMR) AF: 0.762 AC: 11639 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3108 AN: 3472

East Asian (EAS) AF: 0.763 AC: 3938 AN: 5164

South Asian (SAS) AF: 0.938 AC: 4524 AN: 4824

European-Finnish (FIN) AF: 0.769 AC: 8129 AN: 10568

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60332 AN: 67996

Other (OTH) AF: 0.763 AC: 1611 AN: 2112

Alfa AF: 0.836 Hom.: 252078

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

Nov 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.65
DANN	Benign	0.86
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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