Genetic Variant SLCO2B1:p.Gly81Arg (chr11-75164056-G-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_007256.5(SLCO2B1):c.241G>C(p.Gly81Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SLCO2B1
NM_007256.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.52

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO2B1	NM_007256.5 link	c.241G>C	p.Gly81Arg	missense_variant	Exon 3 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.241G>C	p.Gly81Arg	missense_variant	Exon 3 of 14	1	NM_007256.5	ENSP00000289575.5		A0A024R5I4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1455732

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723522

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33332

American (AMR)

AF:

0.00

AC:

AN:

44074

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25952

East Asian (EAS)

AF:

0.00

AC:

AN:

39446

South Asian (SAS)

AF:

0.00

AC:

AN:

84772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52862

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

1109390

Other (OTH)

AF:

0.00

AC:

AN:

60144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 24, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.241G>C (p.G81R) alteration is located in exon 3 (coding exon 3) of the SLCO2B1 gene. This alteration results from a G to C substitution at nucleotide position 241, causing the glycine (G) at amino acid position 81 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

D;D;D;D;.

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.88

D;D;D;D;D

MetaSVM

Uncertain

-0.039

PhyloP100

9.5

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-6.1

D;D;D;D;D

REVEL

Uncertain

0.55

Sift

Uncertain

0.0090

D;D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D;D

Vest4

0.61, 0.57

MutPred

0.58

.;Loss of ubiquitination at K78 (P = 0.0246);.;.;.;

MVP

0.95

MPC

0.93

ClinPred

1.0

GERP RS

4.8

gMVP

0.64

Mutation Taster

=24/76

disease causing

(source)

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

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11-75164056-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over