chr11-75164056-G-C

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

8
8
1

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]

Genome browser will be placed here

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
SLCO2B1NM_007256.5 linkc.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
SLCO2B1ENST00000289575.10 linkc.241G>C p.Gly81Arg missense_variant Exon 3 of 14 1 NM_007256.5 ENSP00000289575.5 A0A024R5I4

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000275
AC:
4
AN:
1455732
Hom.:
0
Cov.:
31
AF XY:
0.00000276
AC XY:
2
AN XY:
723522
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33332
American (AMR)
AF:
0.00
AC:
0
AN:
44074
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25952
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39446
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84772
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52862
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
0.00000361
AC:
4
AN:
1109390
Other (OTH)
AF:
0.00
AC:
0
AN:
60144
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.538
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
31

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
D
BayesDel_noAF
Uncertain
0.080
CADD
Pathogenic
26
DANN
Pathogenic
1.0
Eigen
Pathogenic
0.86
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.97
D;D;D;D;.
M_CAP
Uncertain
0.14
D
MetaRNN
Pathogenic
0.88
D;D;D;D;D
MetaSVM
Uncertain
-0.039
T
PhyloP100
9.5
PrimateAI
Pathogenic
0.80
T
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
D
GERP RS
4.8
gMVP
0.64
Mutation Taster
=24/76
disease causing

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

Other links and lift over

dbSNP: rs750333137; hg19: chr11-74875101; API