2-218262758-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_170699.3(GPBAR1):​c.34C>T​(p.Pro12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,607,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GPBAR1
NM_170699.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.320
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04275304).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPBAR1NM_170699.3 linkc.34C>T p.Pro12Ser missense_variant Exon 2 of 2 ENST00000519574.2 NP_733800.1 Q8TDU6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPBAR1ENST00000519574.2 linkc.34C>T p.Pro12Ser missense_variant Exon 2 of 2 1 NM_170699.3 ENSP00000430202.1 Q8TDU6
GPBAR1ENST00000479077.5 linkc.34C>T p.Pro12Ser missense_variant Exon 2 of 2 2 ENSP00000430698.1 Q8TDU6
GPBAR1ENST00000521462.1 linkc.34C>T p.Pro12Ser missense_variant Exon 2 of 2 2 ENSP00000428824.1 Q8TDU6
GPBAR1ENST00000522678.5 linkc.34C>T p.Pro12Ser missense_variant Exon 2 of 2 2 ENSP00000430886.1 Q8TDU6

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152084
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1455852
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
723514
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152084
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000827
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.061
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
0.84
DANN
Benign
0.69
DEOGEN2
Benign
0.039
T;T;T;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.080
N
LIST_S2
Benign
0.44
.;.;.;T
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.043
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.6
L;L;L;L
PrimateAI
Benign
0.30
T
PROVEAN
Benign
0.13
N;N;N;N
REVEL
Benign
0.014
Sift
Benign
0.16
T;T;T;T
Sift4G
Benign
0.084
T;T;T;T
Polyphen
0.0
B;B;B;B
Vest4
0.13
MutPred
0.11
Gain of glycosylation at P12 (P = 0.0426);Gain of glycosylation at P12 (P = 0.0426);Gain of glycosylation at P12 (P = 0.0426);Gain of glycosylation at P12 (P = 0.0426);
MVP
0.040
MPC
0.044
ClinPred
0.22
T
GERP RS
-1.7
Varity_R
0.043
gMVP
0.43

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: rs747879212; hg19: chr2-219127481; API