rs60571683

Positions:

chr12-20916115-G-A

Variant summary

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

The NM_019844.4(SLCO1B3):c.1977G>A(p.Ser659=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0476 in 1,612,444 control chromosomes in the GnomAD database, including 2,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 177 hom., cov: 32)

Exomes 𝑓: 0.049 ( 2106 hom. )

Consequence

SLCO1B3
NM_019844.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.782

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 12-20916115-G-A is Benign according to our data. Variant chr12-20916115-G-A is described in ClinVar as [Benign]. Clinvar id is 307914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.782 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLCO1B3	NM_019844.4 linkuse as main transcript	c.1977G>A	p.Ser659=	synonymous_variant	16/16	ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1 linkuse as main transcript	c.1865+14648G>A		intron_variant			NP_001358026.1
LOC124902894	XM_047429949.1 linkuse as main transcript	c.-58+14648G>A		intron_variant			XP_047285905.1
SLCO1B3	NM_001349920.2 linkuse as main transcript	c.1893G>A	p.Ser631=	synonymous_variant	14/14		NP_001336849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8 linkuse as main transcript	c.1977G>A	p.Ser659=	synonymous_variant	16/16	2	NM_019844.4	ENSP00000370956	P1	Q9NPD5-1
SLCO1B3	ENST00000261196.6 linkuse as main transcript	c.1977G>A	p.Ser659=	synonymous_variant	14/14	1		ENSP00000261196	P1	Q9NPD5-1

Frequencies

GnomAD3 genomes

AF:

0.0384

AC:

5836

AN:

151990

Hom.:

178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0610

Gnomad ASJ

AF:

0.0971

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00954

Gnomad FIN

AF:

0.0112

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0561

Gnomad OTH

AF:

0.0436

GnomAD3 exomes

AF:

0.0379

AC:

9487

AN:

250602

Hom.:

277

AF XY:

0.0380

AC XY:

5147

AN XY:

135452

show subpopulations

Gnomad AFR exome

AF:

0.00875

Gnomad AMR exome

AF:

0.0390

Gnomad ASJ exome

AF:

0.0874

Gnomad EAS exome

AF:

0.000328

Gnomad SAS exome

AF:

0.00817

Gnomad FIN exome

AF:

0.0123

Gnomad NFE exome

AF:

0.0555

Gnomad OTH exome

AF:

0.0520

GnomAD4 exome

AF:

0.0486

AC:

70986

AN:

1460338

Hom.:

2106

Cov.:

AF XY:

0.0477

AC XY:

34644

AN XY:

726514

show subpopulations

Gnomad4 AFR exome

AF:

0.00804

Gnomad4 AMR exome

AF:

0.0415

Gnomad4 ASJ exome

AF:

0.0897

Gnomad4 EAS exome

AF:

0.000278

Gnomad4 SAS exome

AF:

0.00885

Gnomad4 FIN exome

AF:

0.0144

Gnomad4 NFE exome

AF:

0.0556

Gnomad4 OTH exome

AF:

0.0504

GnomAD4 genome

AF:

0.0383

AC:

5830

AN:

152106

Hom.:

177

Cov.:

AF XY:

0.0361

AC XY:

2683

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.0607

Gnomad4 ASJ

AF:

0.0971

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00954

Gnomad4 FIN

AF:

0.0112

Gnomad4 NFE

AF:

0.0561

Gnomad4 OTH

AF:

0.0427

Alfa

AF:

0.0513

Hom.:

250

Bravo

AF:

0.0415

Asia WGS

AF:

0.00405

AC:

AN:

3474

EpiCase

AF:

0.0595

EpiControl

AF:

0.0643

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Rotor syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 27, 2023	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

SLCO1B3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.5

DANN

Benign

0.41

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