chr11-75165854-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_007256.5(SLCO2B1):​c.353T>C​(p.Ile118Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,461,876 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: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SLCO2B1
NM_007256.5 missense

Scores

8
7
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.61

Publications

2 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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.826

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLCO2B1NM_007256.5 linkc.353T>C p.Ile118Thr missense_variant Exon 4 of 14 ENST00000289575.10 NP_009187.1 O94956A0A024R5I4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLCO2B1ENST00000289575.10 linkc.353T>C p.Ile118Thr missense_variant Exon 4 of 14 1 NM_007256.5 ENSP00000289575.5 A0A024R5I4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251466
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000150
AC:
22
AN:
1461876
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727242
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000189
AC:
21
AN:
1112000
Other (OTH)
AF:
0.00
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.468
Heterozygous variant carriers
0
2
3
5
6
8
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.:
33
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000113
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 21, 2022
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.353T>C (p.I118T) alteration is located in exon 4 (coding exon 4) of the SLCO2B1 gene. This alteration results from a T to C substitution at nucleotide position 353, causing the isoleucine (I) at amino acid position 118 to be replaced by a threonine (T). 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
Pathogenic
0.73
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Pathogenic
0.22
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
.;T;.;.;.;.
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D;T;.;D;D;.
M_CAP
Uncertain
0.15
D
MetaRNN
Pathogenic
0.83
D;D;D;D;D;D
MetaSVM
Benign
-0.48
T
PhyloP100
7.6
PrimateAI
Uncertain
0.65
T
PROVEAN
Pathogenic
-4.8
D;D;N;D;D;D
REVEL
Uncertain
0.56
Sift
Pathogenic
0.0
D;D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D
Vest4
0.94
MVP
0.86
MPC
0.96
ClinPred
1.0
D
GERP RS
4.2
PromoterAI
-0.056
Neutral
gMVP
0.84
Mutation Taster
=40/60
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: rs141178021; hg19: chr11-74876899; API