2-218262962-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_170699.3(GPBAR1):​c.238C>T​(p.Arg80Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,613,796 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 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

GPBAR1
NM_170699.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0650
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13997978).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GPBAR1NM_170699.3 linkuse as main transcriptc.238C>T p.Arg80Trp 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.238C>T p.Arg80Trp missense_variant 2/21 NM_170699.3 ENSP00000430202 P1
GPBAR1ENST00000479077.5 linkuse as main transcriptc.238C>T p.Arg80Trp missense_variant 2/22 ENSP00000430698 P1
GPBAR1ENST00000521462.1 linkuse as main transcriptc.238C>T p.Arg80Trp missense_variant 2/22 ENSP00000428824 P1
GPBAR1ENST00000522678.5 linkuse as main transcriptc.238C>T p.Arg80Trp missense_variant 2/22 ENSP00000430886 P1

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152118
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000290
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000362
AC:
9
AN:
248932
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135074
show subpopulations
Gnomad AFR exome
AF:
0.000323
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000534
AC:
78
AN:
1461678
Hom.:
0
Cov.:
31
AF XY:
0.0000481
AC XY:
35
AN XY:
727118
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000567
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000986
AC:
15
AN:
152118
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.000290
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000217
Hom.:
0
Bravo
AF:
0.000113
ESP6500AA
AF:
0.000230
AC:
1
ESP6500EA
AF:
0.000117
AC:
1
ExAC
AF:
0.0000825
AC:
10

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)Sep 08, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Benign
0.038
T;T;T;T
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.35
FATHMM_MKL
Benign
0.27
N
LIST_S2
Benign
0.69
.;.;.;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.14
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N;N;N;N
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
0.11
N;N;N;N
REVEL
Benign
0.14
Sift
Benign
0.19
T;T;T;T
Sift4G
Uncertain
0.052
T;T;T;T
Polyphen
1.0
D;D;D;D
Vest4
0.19
MVP
0.43
MPC
0.045
ClinPred
0.093
T
GERP RS
3.3
Varity_R
0.099
gMVP
0.48

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: rs200126718; hg19: chr2-219127685; API