12-21239042-A-C

Position:

chr12-21239042-A-C

Variant summary

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

The NM_006446.5(SLCO1B1):c.1929A>C(p.Leu643Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0503 in 1,592,164 control chromosomes in the GnomAD database, including 2,239 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 241 hom., cov: 32)

Exomes 𝑓: 0.050 ( 1998 hom. )

Consequence

SLCO1B1
NM_006446.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.965

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:

LOC124902895 (HGNC:):

LOC124902895 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=0.0016977489).

BP6

Variant 12-21239042-A-C is Benign according to our data. Variant chr12-21239042-A-C is described in ClinVar as [Benign]. Clinvar id is 307959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-21239042-A-C is described in Lovd as [Benign]. Variant chr12-21239042-A-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.062 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.1929A>C	p.Leu643Phe	missense_variant	15/15	ENST00000256958.3	NP_006437.3	Q9Y6L6Q05CV5A0A024RAU7
LOC124902895	XR_007063239.1 linkuse as main transcript	n.87-4743T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3 linkuse as main transcript	c.1929A>C	p.Leu643Phe	missense_variant	15/15	1	NM_006446.5	ENSP00000256958.2		Q9Y6L6

Frequencies

GnomAD3 genomes

AF:

0.0534

AC:

8124

AN:

152044

Hom.:

238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0639

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.0491

Gnomad ASJ

AF:

0.0588

Gnomad EAS

AF:

0.00250

Gnomad SAS

AF:

0.0529

Gnomad FIN

AF:

0.0347

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0536

Gnomad OTH

AF:

0.0583

GnomAD3 exomes

AF:

0.0453

AC:

11209

AN:

247440

Hom.:

285

AF XY:

0.0461

AC XY:

6186

AN XY:

134330

show subpopulations

Gnomad AFR exome

AF:

0.0661

Gnomad AMR exome

AF:

0.0355

Gnomad ASJ exome

AF:

0.0634

Gnomad EAS exome

AF:

0.000988

Gnomad SAS exome

AF:

0.0449

Gnomad FIN exome

AF:

0.0394

Gnomad NFE exome

AF:

0.0523

Gnomad OTH exome

AF:

0.0447

GnomAD4 exome

AF:

0.0500

AC:

72012

AN:

1440000

Hom.:

1998

Cov.:

AF XY:

0.0503

AC XY:

36059

AN XY:

717384

show subpopulations

Gnomad4 AFR exome

AF:

0.0660

Gnomad4 AMR exome

AF:

0.0353

Gnomad4 ASJ exome

AF:

0.0628

Gnomad4 EAS exome

AF:

0.000533

Gnomad4 SAS exome

AF:

0.0457

Gnomad4 FIN exome

AF:

0.0406

Gnomad4 NFE exome

AF:

0.0523

Gnomad4 OTH exome

AF:

0.0513

GnomAD4 genome

AF:

0.0535

AC:

8137

AN:

152164

Hom.:

241

Cov.:

AF XY:

0.0526

AC XY:

3913

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0641

Gnomad4 AMR

AF:

0.0489

Gnomad4 ASJ

AF:

0.0588

Gnomad4 EAS

AF:

0.00251

Gnomad4 SAS

AF:

0.0529

Gnomad4 FIN

AF:

0.0347

Gnomad4 NFE

AF:

0.0535

Gnomad4 OTH

AF:

0.0577

Alfa

AF:

0.0527

Hom.:

329

Bravo

AF:

0.0539

TwinsUK

AF:

0.0566

AC:

210

ALSPAC

AF:

0.0547

AC:

211

ESP6500AA

AF:

0.0635

AC:

277

ESP6500EA

AF:

0.0559

AC:

478

ExAC

AF:

0.0452

AC:

5481

Asia WGS

AF:

0.0370

AC:

129

AN:

3472

EpiCase

AF:

0.0590

EpiControl

AF:

0.0584

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	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. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 27, 2023	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	This variant is associated with the following publications: (PMID: 22147369) -
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

0.093

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.20

DANN

Benign

0.26

DEOGEN2

Benign

0.044

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0052

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.090

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.27

REVEL

Benign

0.014

Sift

Benign

0.63

Sift4G

Benign

0.34

Polyphen

0.0020

Vest4

0.039

MutPred

0.20

Gain of methylation at K648 (P = 0.0775);

MPC

0.010

ClinPred

0.0028

GERP RS

-2.6

Varity_R

0.056

gMVP

0.16

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