11-75172532-G-A

Variant names:

• chr11-75172532-G-A
• rs12422149
• NM_007256.5:c.935G>A

Variant summary

Our verdict is Benign. The variant received -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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 123 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007256.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO2B1	NM_007256.5	MANE Select	c.935G>A	p.Arg312Gln	missense	Exon 7 of 14	NP_009187.1
	SLCO2B1	NM_001145211.3		c.869G>A	p.Arg290Gln	missense	Exon 7 of 14	NP_001138683.1
	SLCO2B1	NM_001145212.3		c.503G>A	p.Arg168Gln	missense	Exon 4 of 11	NP_001138684.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO2B1	ENST00000289575.10	TSL:1 MANE Select	c.935G>A	p.Arg312Gln	missense	Exon 7 of 14	ENSP00000289575.5
	SLCO2B1	ENST00000428359.6	TSL:1	c.869G>A	p.Arg290Gln	missense	Exon 7 of 14	ENSP00000388912.2
	SLCO2B1	ENST00000532236.5	TSL:2	c.587G>A	p.Arg196Gln	missense	Exon 5 of 12	ENSP00000434112.1

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

GnomAD2 exomes AF: 0.184 AC: 46135 AN: 251382 AF XY: 0.174

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

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

GnomAD4 genome AF: 0.130 AC: 19756 AN: 152204 Hom.: 1775 Cov.: 32 AF XY: 0.135 AC XY: 10068 AN XY: 74416

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: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0979 AC: 6658 AN: 68004

Other (OTH) AF: 0.134 AC: 283 AN: 2114

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.17
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.026
Sift	Benign	0.19	T
Sift4G	Benign	0.51	T
Vest4		0.025
MPC		0.27
ClinPred		0.0040	T
GERP RS		-2.2
gMVP		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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