dbSNP rs12422149: SLCO2B1:p.Arg312Gln (chr11-75172532-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007256.5(SLCO2B1):c.935G>A(p.Arg312Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,613,902 control chromosomes in the GnomAD database, including 17,529 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1775 hom., cov: 32)

Exomes 𝑓: 0.12 ( 15754 hom. )

Consequence

SLCO2B1
NM_007256.5 missense

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -0.165

Variant links:

Genes affected

SLCO2B1 (HGNC:10962): (solute carrier organic anion transporter family member 2B1) This locus encodes a member of the organic anion-transporting polypeptide family of membrane proteins. The protein encoded by this locus may function in regulation of placental uptake of sulfated steroids. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2010]

SLCO2B1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033207834).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO2B1	NM_007256.5 link	c.935G>A	p.Arg312Gln	missense_variant	Exon 7 of 14	ENST00000289575.10	NP_009187.1	O94956A0A024R5I4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO2B1	ENST00000289575.10 link	c.935G>A	p.Arg312Gln	missense_variant	Exon 7 of 14	1	NM_007256.5	ENSP00000289575.5		A0A024R5I4

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19732

AN:

152086

Hom.:

1766

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0917

Gnomad AMI

AF:

0.0659

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0979

Gnomad OTH

AF:

0.133

GnomAD3 exomes

AF:

0.184

AC:

46135

AN:

251382

Hom.:

6299

AF XY:

0.174

AC XY:

23705

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.0957

Gnomad AMR exome

AF:

0.435

Gnomad ASJ exome

AF:

0.131

Gnomad EAS exome

AF:

0.327

Gnomad SAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.105

Gnomad OTH exome

AF:

0.162

GnomAD4 exome

AF:

0.124

AC:

181431

AN:

1461698

Hom.:

15754

Cov.:

AF XY:

0.125

AC XY:

90796

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.0921

Gnomad4 AMR exome

AF:

0.423

Gnomad4 ASJ exome

AF:

0.124

Gnomad4 EAS exome

AF:

0.353

Gnomad4 SAS exome

AF:

0.215

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.0973

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.130

AC:

19756

AN:

152204

Hom.:

1775

Cov.:

AF XY:

0.135

AC XY:

10068

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0917

Gnomad4 AMR

AF:

0.286

Gnomad4 ASJ

AF:

0.129

Gnomad4 EAS

AF:

0.335

Gnomad4 SAS

AF:

0.237

Gnomad4 FIN

AF:

0.115

Gnomad4 NFE

AF:

0.0979

Gnomad4 OTH

AF:

0.134

Alfa

AF:

0.113

Hom.:

3394

Bravo

AF:

0.144

TwinsUK

AF:

0.104

AC:

385

ALSPAC

AF:

0.0882

AC:

340

ESP6500AA

AF:

0.0930

AC:

409

ESP6500EA

AF:

0.101

AC:

869

ExAC

AF:

0.173

AC:

21028

Asia WGS

AF:

0.327

AC:

1136

AN:

3478

EpiCase

AF:

0.103

EpiControl

AF:

0.0994

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Atorvastatin response

Other:1

Apr 13, 2022

Pharmacometrics, Pharmacogenomics, Pharmacokinetics Research Group, Catholic University of Louvain

Significance: drug response

Review Status: no assertion criteria provided

Collection Method: in vitro

functional variant -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0030

.;T;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.84

T;T;T;.;.

MetaRNN

Benign

0.0033

T;T;T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.34

N;N;N;N;N

REVEL

Benign

0.026

Sift

Benign

0.19

T;T;T;T;T

Sift4G

Benign

0.51

T;T;T;T;T

Vest4

0.025

MPC

0.27

ClinPred

0.0040

GERP RS

-2.2

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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