rs2306168

chr11-75196537-C-T

Variant summary

Our verdict is Benign. Variant got -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. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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=0.0051302314).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO2B1	NM_007256.5	c.1457C>T	p.Ser486Phe	missense_variant	10/14	ENST00000289575.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO2B1	ENST00000289575.10	c.1457C>T	p.Ser486Phe	missense_variant	10/14	1	NM_007256.5	P2

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

GnomAD3 exomes AF: 0.0775 AC: 19444 AN: 250876 Hom.: 1745 AF XY: 0.0696 AC XY: 9441 AN XY: 135656

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 SAS exome AF: 0.0627

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

Gnomad4 AFR exome AF: 0.343

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.0517

Gnomad4 EAS exome AF: 0.276

Gnomad4 SAS exome AF: 0.0626

Gnomad4 FIN exome AF: 0.0356

Gnomad4 NFE exome AF: 0.0225

Gnomad4 OTH exome AF: 0.0640

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

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.0992

Gnomad4 ASJ AF: 0.0550

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.0633

Gnomad4 FIN AF: 0.0374

Gnomad4 NFE AF: 0.0239

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0460 Hom.: 677

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 v4.3

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
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.47	T;T;T;.;.
MetaRNN	Benign	0.0051	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
PrimateAI	Benign	0.44	T
PROVEAN	Benign	1.8	N;N;N;N;N
REVEL	Benign	0.022
Sift	Benign	0.71	T;T;T;T;T
Sift4G	Benign	0.72	T;T;T;T;T
Vest4		0.12
MPC		0.25
ClinPred		0.0014	T
GERP RS		3.0
gMVP		0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs2306168; hg19: chr11-74907582; COSMIC: COSV56932809; COSMIC: COSV56932809;