rs2306168

Variant names:

• chr11-75196537-C-T
• rs2306168
• NM_007256.5:c.1457C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007256.5(SLCO2B1):​c.1457C>T​(p.Ser486Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 1,613,876 control chromosomes in the GnomAD database, including 7,253 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 0.13 (2574 hom., cov: 33)
  • Exomes 𝑓: 0.044 (4679 hom.)
• Consequence: SLCO2B1 NM_007256.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.694
• Publications: 69 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=0.0051302314).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO2B1	NM_007256.5	MANE Select	c.1457C>T	p.Ser486Phe	missense	Exon 10 of 14	NP_009187.1
	SLCO2B1	NM_001145211.3		c.1391C>T	p.Ser464Phe	missense	Exon 10 of 14	NP_001138683.1
	SLCO2B1	NM_001145212.3		c.1025C>T	p.Ser342Phe	missense	Exon 7 of 11	NP_001138684.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO2B1	ENST00000289575.10	TSL:1 MANE Select	c.1457C>T	p.Ser486Phe	missense	Exon 10 of 14	ENSP00000289575.5
	SLCO2B1	ENST00000428359.6	TSL:1	c.1391C>T	p.Ser464Phe	missense	Exon 10 of 14	ENSP00000388912.2
	SLCO2B1	ENST00000891032.1		c.1457C>T	p.Ser486Phe	missense	Exon 10 of 15	ENSP00000561091.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19178 AN: 152124 Hom.: 2563 Cov.: 33

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0991

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.0631

Gnomad FIN AF: 0.0374

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0239

Gnomad OTH AF: 0.101

GnomAD2 exomes AF: 0.0775 AC: 19444 AN: 250876 AF XY: 0.0696

Gnomad AFR exome AF: 0.340

Gnomad AMR exome AF: 0.100

Gnomad ASJ exome AF: 0.0542

Gnomad EAS exome AF: 0.225

Gnomad FIN exome AF: 0.0352

Gnomad NFE exome AF: 0.0245

Gnomad OTH exome AF: 0.0554

GnomAD4 exome AF: 0.0443 AC: 64681 AN: 1461634 Hom.: 4679 Cov.: 31 AF XY: 0.0435 AC XY: 31604 AN XY: 727122

African (AFR) AF: 0.343 AC: 11485 AN: 33472

American (AMR) AF: 0.100 AC: 4473 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0517 AC: 1352 AN: 26126

East Asian (EAS) AF: 0.276 AC: 10949 AN: 39696

South Asian (SAS) AF: 0.0626 AC: 5400 AN: 86238

European-Finnish (FIN) AF: 0.0356 AC: 1898 AN: 53312

Middle Eastern (MID) AF: 0.0482 AC: 278 AN: 5768

European-Non Finnish (NFE) AF: 0.0225 AC: 24982 AN: 1111920

Other (OTH) AF: 0.0640 AC: 3864 AN: 60388

GnomAD4 genome AF: 0.126 AC: 19230 AN: 152242 Hom.: 2574 Cov.: 33 AF XY: 0.126 AC XY: 9384 AN XY: 74458

African (AFR) AF: 0.329 AC: 13651 AN: 41506

American (AMR) AF: 0.0992 AC: 1517 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 191 AN: 3470

East Asian (EAS) AF: 0.250 AC: 1292 AN: 5176

South Asian (SAS) AF: 0.0633 AC: 306 AN: 4832

European-Finnish (FIN) AF: 0.0374 AC: 397 AN: 10622

Middle Eastern (MID) AF: 0.0479 AC: 14 AN: 292

European-Non Finnish (NFE) AF: 0.0239 AC: 1626 AN: 68022

Other (OTH) AF: 0.105 AC: 222 AN: 2116

Alfa AF: 0.0628 Hom.: 2959

Bravo AF: 0.140

TwinsUK AF: 0.0208 AC: 77

ALSPAC AF: 0.0208 AC: 80

ESP6500AA AF: 0.331 AC: 1457

ESP6500EA AF: 0.0254 AC: 218

ExAC AF: 0.0802 AC: 9732

Asia WGS AF: 0.176 AC: 610 AN: 3478

EpiCase AF: 0.0254

EpiControl AF: 0.0256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.091
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.69
PrimateAI	Benign	0.44	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.022
Sift	Benign	0.71	T
Sift4G	Benign	0.72	T
Vest4		0.12
MPC		0.25
ClinPred		0.0014	T
GERP RS		3.0
gMVP		0.54
Mutation Taster		=99/1	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: rs2306168; hg19: chr11-74907582; COSMIC: COSV56932809; COSMIC: COSV56932809;