2-218262959-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_170699.3(GPBAR1):​c.235C>T​(p.Arg79Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

GPBAR1
NM_170699.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.173
Variant links:
Genes affected
GPBAR1 (HGNC:19680): (G protein-coupled bile acid receptor 1) This gene encodes a member of the G protein-coupled receptor (GPCR) superfamily. This enzyme functions as a cell surface receptor for bile acids. Treatment of cells expressing this GPCR with bile acids induces the production of intracellular cAMP, activation of a MAP kinase signaling pathway, and internalization of the receptor. The receptor is implicated in the suppression of macrophage functions and regulation of energy homeostasis by bile acids. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31371477).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GPBAR1NM_170699.3 linkuse as main transcriptc.235C>T p.Arg79Cys missense_variant 2/2 ENST00000519574.2 NP_733800.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GPBAR1ENST00000519574.2 linkuse as main transcriptc.235C>T p.Arg79Cys missense_variant 2/21 NM_170699.3 ENSP00000430202 P1
GPBAR1ENST00000479077.5 linkuse as main transcriptc.235C>T p.Arg79Cys missense_variant 2/22 ENSP00000430698 P1
GPBAR1ENST00000521462.1 linkuse as main transcriptc.235C>T p.Arg79Cys missense_variant 2/22 ENSP00000428824 P1
GPBAR1ENST00000522678.5 linkuse as main transcriptc.235C>T p.Arg79Cys missense_variant 2/22 ENSP00000430886 P1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152152
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000321
AC:
8
AN:
248904
Hom.:
0
AF XY:
0.0000518
AC XY:
7
AN XY:
135048
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000111
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000355
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000356
AC:
52
AN:
1461668
Hom.:
0
Cov.:
31
AF XY:
0.0000275
AC XY:
20
AN XY:
727116
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000351
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152270
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000412
AC:
5
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Nov 08, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T;T;T;T
Eigen
Benign
0.036
Eigen_PC
Benign
-0.022
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.80
.;.;.;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.31
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
L;L;L;L
MutationTaster
Benign
0.73
N;N;N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.6
N;N;N;N
REVEL
Benign
0.24
Sift
Uncertain
0.026
D;D;D;D
Sift4G
Uncertain
0.027
D;D;D;D
Polyphen
0.99
D;D;D;D
Vest4
0.39
MutPred
0.67
Loss of MoRF binding (P = 0.1715);Loss of MoRF binding (P = 0.1715);Loss of MoRF binding (P = 0.1715);Loss of MoRF binding (P = 0.1715);
MVP
0.57
MPC
0.23
ClinPred
0.27
T
GERP RS
4.2
Varity_R
0.098
gMVP
0.47

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: rs199822804; hg19: chr2-219127682; COSMIC: COSV99946277; COSMIC: COSV99946277; API