rs12422149

chr11-75172532-G-Achr11-75172532-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.13 (1775 hom., cov: 32)
  • Exomes 𝑓: 0.12 (15754 hom.)
• Consequence: SLCO2B1 NM_007256.5 missense
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.165

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]

ACMG classification

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/exons	MANE	UniProt
SLCO2B1	NM_007256.5	c.935G>A	p.Arg312Gln	missense_variant	7/14	ENST00000289575.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO2B1	ENST00000289575.10	c.935G>A	p.Arg312Gln	missense_variant	7/14	1	NM_007256.5	P2

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19732 AN: 152086 Hom.: 1766 Cov.: 32

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

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.: 32 AF XY: 0.125 AC XY: 90796 AN XY: 727148

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.: 32 AF XY: 0.135 AC XY: 10068 AN XY: 74416

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

Submissions by phenotype

Atorvastatin response Other:1

drug response, no assertion criteria provided

in vitro

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

Apr 13, 2022

functional variant -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	10
Dann	Benign	0.96
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.84	T;T;T;.;.
MetaRNN	Benign	0.0033	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
PrimateAI	Benign	0.24	T
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	T
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

Other links and lift over

dbSNP: rs12422149; hg19: chr11-74883577; COSMIC: COSV56938612; COSMIC: COSV56938612;