Genetic Variant NM_007256.5:c.935G>A (chr11-75172532-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.13 ( 1775 hom., cov: 32)

Exomes 𝑓: 0.12 ( 15754 hom. )

Consequence

SLCO2B1
NM_007256.5 missense

Scores

Clinical Significance

- - O:1

Conservation

PhyloP100: -0.165

Publications

123 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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

GnomAD2 exomes

AF:

0.184

AC:

46135

AN:

251382

AF XY:

0.174

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 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

African (AFR)

AF:

0.0921

AC:

3082

AN:

33474

American (AMR)

AF:

0.423

AC:

18909

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

3242

AN:

26132

East Asian (EAS)

AF:

0.353

AC:

13995

AN:

39694

South Asian (SAS)

AF:

0.215

AC:

18550

AN:

86242

European-Finnish (FIN)

AF:

0.121

AC:

6477

AN:

53402

Middle Eastern (MID)

AF:

0.145

AC:

834

AN:

5768

European-Non Finnish (NFE)

AF:

0.0973

AC:

108183

AN:

1111876

Other (OTH)

AF:

0.135

AC:

8159

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

7723

15446

23168

30891

38614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4324

8648

12972

17296

21620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.130

AC:

19756

AN:

152204

Hom.:

1775

Cov.:

AF XY:

0.135

AC XY:

10068

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0917

AC:

3808

AN:

41536

American (AMR)

AF:

0.286

AC:

4370

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

446

AN:

3470

East Asian (EAS)

AF:

0.335

AC:

1737

AN:

5178

South Asian (SAS)

AF:

0.237

AC:

1141

AN:

4824

European-Finnish (FIN)

AF:

0.115

AC:

1217

AN:

10594

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0979

AC:

6658

AN:

68004

Other (OTH)

AF:

0.134

AC:

283

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

828

1656

2484

3312

4140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.116

Hom.:

6954

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: -

Submissions summary: Other:1

Revision: -

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

(source)

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

PhyloP100

-0.17

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over