Genetic Variant NM_007256.5:c.43C>T (chr11-75162681-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_007256.5(SLCO2B1):c.43C>T(p.Pro15Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000317 in 1,613,796 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.0016 ( 3 hom., cov: 31)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

SLCO2B1
NM_007256.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0640

Publications

6 publications found

Variant links:

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]

SLCO2B1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006646633).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO2B1	NM_007256.5 link	c.43C>T	p.Pro15Ser	missense_variant	Exon 2 of 14	ENST00000289575.10	NP_009187.1	O94956A0A024R5I4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO2B1	ENST00000289575.10 link	c.43C>T	p.Pro15Ser	missense_variant	Exon 2 of 14	1	NM_007256.5	ENSP00000289575.5		A0A024R5I4

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

247

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00539

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.000458

AC:

115

AN:

251102

AF XY:

0.000376

show subpopulations

Gnomad AFR exome

AF:

0.00455

Gnomad AMR exome

AF:

0.000957

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000179

AC:

262

AN:

1461660

Hom.:

Cov.:

AF XY:

0.000166

AC XY:

121

AN XY:

727146

show subpopulations

African (AFR)

AF:

0.00499

AC:

167

AN:

33472

American (AMR)

AF:

0.00110

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1111894

Other (OTH)

AF:

0.000381

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00164

AC:

249

AN:

152136

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

118

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00542

AC:

225

AN:

41504

American (AMR)

AF:

0.00124

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68008

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000632

Hom.:

Bravo

AF:

0.00175

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000469

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.6

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.69

M_CAP

Benign

0.019

MetaRNN

Benign

0.0066

MetaSVM

Benign

-0.83

PhyloP100

-0.064

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.95

REVEL

Benign

0.11

Sift

Uncertain

0.013

Sift4G

Uncertain

0.033

Vest4

0.25

MVP

0.61

MPC

0.26

ClinPred

0.019

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.34

Mutation Taster

=298/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over