Variant chr12-20901435-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_019844.4(SLCO1B3):c.1833G>A(p.Gly611=) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.38

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:):

SLCO1B3-SLCO1B7 links:

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ACMG classification

Classification made for transcript

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
SLCO1B3	NM_019844.4 linkuse as main transcript	c.1833G>A	p.Gly611=	synonymous_variant	15/16	ENST00000381545.8
SLCO1B3-SLCO1B7	NM_001371097.1 linkuse as main transcript	c.1833G>A	p.Gly611=	synonymous_variant	13/16
LOC124902894	XM_047429949.1 linkuse as main transcript	c.-90G>A		5_prime_UTR_variant	1/10
SLCO1B3	NM_001349920.2 linkuse as main transcript	c.1749G>A	p.Gly583=	synonymous_variant	13/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1B3	ENST00000381545.8 linkuse as main transcript	c.1833G>A	p.Gly611=	synonymous_variant	15/16	2	NM_019844.4	P1	Q9NPD5-1
SLCO1B3	ENST00000261196.6 linkuse as main transcript	c.1833G>A	p.Gly611=	synonymous_variant	13/14	1		P1	Q9NPD5-1
SLCO1B3	ENST00000544370.1 linkuse as main transcript	c.1305G>A	p.Gly435=	synonymous_variant	9/10	5

Frequencies

GnomAD3 genomes

AF:

0.714

AC:

108446

AN:

151900

Hom.:

42953

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.873

AC XY:

611656

AN XY:

700460

show subpopulations

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.:

AF XY:

0.712

AC XY:

52881

AN XY:

74322

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Rotor syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -

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

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