rs11045819

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006446.5(SLCO1B1):c.463C>A(p.Pro155Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,507,068 control chromosomes in the GnomAD database, including 11,786 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P155L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.12 ( 1313 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10473 hom. )

Consequence

SLCO1B1
NM_006446.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.805

Variant links:

Genes affected

SLCO1B1 (HGNC:10959): (solute carrier organic anion transporter family member 1B1) 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 numerous endogenous compounds including bilirubin, 17-beta-glucuronosyl estradiol and leukotriene C4. This protein is also involved in the removal of drug compounds such as statins, bromosulfophthalein and rifampin from the blood into the hepatocytes. Polymorphisms in the gene encoding this protein are associated with impaired transporter function. [provided by RefSeq, Mar 2009]

SLCO1B1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021197796).

BP6

Variant 12-21176879-C-A is Benign according to our data. Variant chr12-21176879-C-A is described in ClinVar as [Benign]. Clinvar id is 307937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-21176879-C-A is described in Lovd as [Benign]. Variant chr12-21176879-C-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1B1	NM_006446.5 linkuse as main transcript	c.463C>A	p.Pro155Thr	missense_variant	5/15	ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3 linkuse as main transcript	c.463C>A	p.Pro155Thr	missense_variant	5/15	1	NM_006446.5	ENSP00000256958	P1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18260

AN:

151792

Hom.:

1314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0785

Gnomad AMI

AF:

0.414

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0414

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.113

GnomAD3 exomes

AF:

0.114

AC:

28564

AN:

250104

Hom.:

2073

AF XY:

0.115

AC XY:

15611

AN XY:

135230

show subpopulations

Gnomad AFR exome

AF:

0.0766

Gnomad AMR exome

AF:

0.0702

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.0432

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.163

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.110

AC:

148526

AN:

1355158

Hom.:

10473

Cov.:

AF XY:

0.108

AC XY:

73343

AN XY:

677414

show subpopulations

Gnomad4 AFR exome

AF:

0.0632

Gnomad4 AMR exome

AF:

0.0670

Gnomad4 ASJ exome

AF:

0.176

Gnomad4 EAS exome

AF:

0.000279

Gnomad4 SAS exome

AF:

0.0409

Gnomad4 FIN exome

AF:

0.0931

Gnomad4 NFE exome

AF:

0.123

Gnomad4 OTH exome

AF:

0.105

GnomAD4 genome

AF:

0.120

AC:

18261

AN:

151910

Hom.:

1313

Cov.:

AF XY:

0.115

AC XY:

8524

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.0785

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.212

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0416

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.159

Gnomad4 OTH

AF:

0.111

Alfa

AF:

0.145

Hom.:

2888

Bravo

AF:

0.121

TwinsUK

AF:

0.169

AC:

627

ALSPAC

AF:

0.158

AC:

609

ESP6500AA

AF:

0.0860

AC:

379

ESP6500EA

AF:

0.161

AC:

1379

ExAC

AF:

0.117

AC:

14142

Asia WGS

AF:

0.0240

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Rotor syndrome

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 27, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 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. -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

SLCO1B1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 21, 2021

This variant is classified as likely 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

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.2

DANN

Benign

0.69

DEOGEN2

Benign

0.035

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.025

Sift

Benign

0.16

Sift4G

Benign

0.47

Polyphen

0.0020

Vest4

0.10

MPC

0.012

ClinPred

0.0024

GERP RS

-3.4

Varity_R

0.11

gMVP

0.29

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