2-218262724-G-A

Variant summary

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

The NM_170699.3(GPBAR1):​c.-1G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000444 in 1,578,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

GPBAR1
NM_170699.3 5_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 1.44
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 (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GPBAR1NM_170699.3 linkuse as main transcriptc.-1G>A 5_prime_UTR_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.-1G>A 5_prime_UTR_variant 2/21 NM_170699.3 ENSP00000430202 P1
GPBAR1ENST00000479077.5 linkuse as main transcriptc.-1G>A 5_prime_UTR_variant 2/22 ENSP00000430698 P1
GPBAR1ENST00000521462.1 linkuse as main transcriptc.-1G>A 5_prime_UTR_variant 2/22 ENSP00000428824 P1
GPBAR1ENST00000522678.5 linkuse as main transcriptc.-1G>A 5_prime_UTR_variant 2/22 ENSP00000430886 P1

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152106
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.0000544
AC:
12
AN:
220606
Hom.:
0
AF XY:
0.0000249
AC XY:
3
AN XY:
120368
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000928
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:
0.0000792
Gnomad OTH exome
AF:
0.000186
GnomAD4 exome
AF:
0.0000393
AC:
56
AN:
1426040
Hom.:
0
Cov.:
31
AF XY:
0.0000411
AC XY:
29
AN XY:
705092
show subpopulations
Gnomad4 AFR exome
AF:
0.000273
Gnomad4 AMR exome
AF:
0.000117
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000121
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000192
Gnomad4 OTH exome
AF:
0.000187
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152224
Hom.:
0
Cov.:
32
AF XY:
0.000107
AC XY:
8
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000147
Hom.:
0
Bravo
AF:
0.000102

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1Benign: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)Jul 06, 2018- -
GPBAR1-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesDec 09, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
12
DANN
Benign
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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: rs200558126; hg19: chr2-219127447; API