chr12-21172717-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_006446.5(SLCO1B1):​c.152C>T​(p.Ser51Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000849 in 1,613,190 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000080 ( 1 hom. )

Consequence

SLCO1B1
NM_006446.5 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.886
Variant links:
Genes affected
SLCO1B1 (HGNC:10959): (solute carrier organic anion transporter family member 1B1) This gene encodes a liver-specific member of the organic anion transporter family. The encoded protein is a transmembrane receptor that mediates the sodium-independent uptake of numerous endogenous compounds including bilirubin, 17-beta-glucuronosyl estradiol and leukotriene C4. This protein is also involved in the removal of drug compounds such as statins, bromosulfophthalein and rifampin from the blood into the hepatocytes. Polymorphisms in the gene encoding this protein are associated with impaired transporter function. [provided by RefSeq, Mar 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.33137524).
BS2
High AC in GnomAd4 at 20 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLCO1B1NM_006446.5 linkuse as main transcriptc.152C>T p.Ser51Phe missense_variant 3/15 ENST00000256958.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLCO1B1ENST00000256958.3 linkuse as main transcriptc.152C>T p.Ser51Phe missense_variant 3/151 NM_006446.5 P1

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152140
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000111
AC:
28
AN:
251136
Hom.:
0
AF XY:
0.0000884
AC XY:
12
AN XY:
135758
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00179
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000801
AC:
117
AN:
1460932
Hom.:
1
Cov.:
31
AF XY:
0.0000798
AC XY:
58
AN XY:
726822
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00161
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000333
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152258
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000171
Hom.:
0
Bravo
AF:
0.000113
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

Rotor syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesOct 11, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.65
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
T
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.59
T
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.33
T
MetaSVM
Uncertain
-0.21
T
MutationAssessor
Pathogenic
3.6
H
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.46
T
PROVEAN
Pathogenic
-5.3
D
REVEL
Uncertain
0.37
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0030
D
Polyphen
0.96
P
Vest4
0.57
MVP
0.63
MPC
0.065
ClinPred
0.79
D
GERP RS
3.4
Varity_R
0.77
gMVP
0.72

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs769900186; hg19: chr12-21325651; COSMIC: COSV57009899; API