chr11-75169325-G-A

Variant names:

• chr11-75169325-G-A
• rs35199625
• NM_007256.5:c.601G>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.601G>A​(p.Val201Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,614,034 control chromosomes in the GnomAD database, including 301 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.013 (27 hom., cov: 32)
  • Exomes 𝑓: 0.015 (274 hom.)
• Consequence: SLCO2B1 NM_007256.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42
• Publications: 22 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=0.008726269).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0574 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.601G>A	p.Val201Met	missense	Exon 5 of 14	NP_009187.1
	SLCO2B1	NM_001145211.3		c.535G>A	p.Val179Met	missense	Exon 5 of 14	NP_001138683.1
	SLCO2B1	NM_001145212.3		c.169G>A	p.Val57Met	missense	Exon 2 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.601G>A	p.Val201Met	missense	Exon 5 of 14	ENSP00000289575.5
	SLCO2B1	ENST00000428359.6	TSL:1	c.535G>A	p.Val179Met	missense	Exon 5 of 14	ENSP00000388912.2
	SLCO2B1	ENST00000532236.5	TSL:2	c.253G>A	p.Val85Met	missense	Exon 3 of 12	ENSP00000434112.1

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1958 AN: 152182 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.00292

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.0627

Gnomad SAS AF: 0.0392

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.0208 AC: 5224 AN: 251208 AF XY: 0.0209

Gnomad AFR exome AF: 0.00252

Gnomad AMR exome AF: 0.0268

Gnomad ASJ exome AF: 0.0199

Gnomad EAS exome AF: 0.0578

Gnomad FIN exome AF: 0.0203

Gnomad NFE exome AF: 0.0128

Gnomad OTH exome AF: 0.0191

GnomAD4 exome AF: 0.0151 AC: 22010 AN: 1461734 Hom.: 274 Cov.: 31 AF XY: 0.0156 AC XY: 11318 AN XY: 727156

African (AFR) AF: 0.00206 AC: 69 AN: 33480

American (AMR) AF: 0.0249 AC: 1112 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0181 AC: 474 AN: 26134

East Asian (EAS) AF: 0.0621 AC: 2464 AN: 39696

South Asian (SAS) AF: 0.0317 AC: 2730 AN: 86244

European-Finnish (FIN) AF: 0.0200 AC: 1070 AN: 53368

Middle Eastern (MID) AF: 0.00711 AC: 41 AN: 5768

European-Non Finnish (NFE) AF: 0.0117 AC: 12985 AN: 1111932

Other (OTH) AF: 0.0176 AC: 1065 AN: 60394

GnomAD4 genome AF: 0.0129 AC: 1960 AN: 152300 Hom.: 27 Cov.: 32 AF XY: 0.0144 AC XY: 1073 AN XY: 74466

African (AFR) AF: 0.00291 AC: 121 AN: 41566

American (AMR) AF: 0.0163 AC: 249 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 64 AN: 3472

East Asian (EAS) AF: 0.0631 AC: 326 AN: 5168

South Asian (SAS) AF: 0.0390 AC: 188 AN: 4822

European-Finnish (FIN) AF: 0.0207 AC: 220 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0112 AC: 763 AN: 68026

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.0134 Hom.: 101

Bravo AF: 0.0125

TwinsUK AF: 0.0119 AC: 44

ALSPAC AF: 0.0125 AC: 48

ESP6500AA AF: 0.00364 AC: 16

ESP6500EA AF: 0.0104 AC: 89

ExAC AF: 0.0204 AC: 2474

Asia WGS AF: 0.0590 AC: 203 AN: 3478

EpiCase AF: 0.0113

EpiControl AF: 0.0112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Benign	0.071
Eigen_PC	Benign	-0.013
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.94	D
MetaRNN	Benign	0.0087	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.4
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Vest4		0.22
MPC		0.83
ClinPred		0.021	T
GERP RS		3.0
gMVP		0.58
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35199625; hg19: chr11-74880370; COSMIC: COSV56935940; COSMIC: COSV56935940;