Variant 2-218262694-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_170699.3(GPBAR1):c.-31G>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 0.00517 in 1,520,630 control chromosomes in the GnomAD database, including 297 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.025 ( 138 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 159 hom. )

Consequence

GPBAR1
NM_170699.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.458

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]

GPBAR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPBAR1	NM_170699.3 linkuse as main transcript	c.-31G>A		5_prime_UTR_variant	2/2	ENST00000519574.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
GPBAR1	ENST00000519574.2 linkuse as main transcript	c.-31G>A	5_prime_UTR_variant	2/2	1	NM_170699.3	P1
GPBAR1	ENST00000479077.5 linkuse as main transcript	c.-31G>A	5_prime_UTR_variant	2/2	2		P1
GPBAR1	ENST00000521462.1 linkuse as main transcript	c.-31G>A	5_prime_UTR_variant	2/2	2		P1
GPBAR1	ENST00000522678.5 linkuse as main transcript	c.-31G>A	5_prime_UTR_variant	2/2	2		P1

Frequencies

GnomAD3 genomes

AF:

0.0252

AC:

3829

AN:

151980

Hom.:

138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0857

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.0226

GnomAD3 exomes

AF:

0.00705

AC:

1163

AN:

165018

Hom.:

AF XY:

0.00563

AC XY:

503

AN XY:

89346

show subpopulations

Gnomad AFR exome

AF:

0.0853

Gnomad AMR exome

AF:

0.00423

Gnomad ASJ exome

AF:

0.00496

Gnomad EAS exome

AF:

0.0000676

Gnomad SAS exome

AF:

0.000172

Gnomad FIN exome

AF:

0.000121

Gnomad NFE exome

AF:

0.000607

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00294

AC:

4024

AN:

1368532

Hom.:

159

Cov.:

AF XY:

0.00262

AC XY:

1761

AN XY:

671276

show subpopulations

Gnomad4 AFR exome

AF:

0.0932

Gnomad4 AMR exome

AF:

0.00475

Gnomad4 ASJ exome

AF:

0.00558

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000231

Gnomad4 FIN exome

AF:

0.000105

Gnomad4 NFE exome

AF:

0.000339

Gnomad4 OTH exome

AF:

0.00718

GnomAD4 genome

AF:

0.0252

AC:

3840

AN:

152098

Hom.:

138

Cov.:

AF XY:

0.0241

AC XY:

1793

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0858

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000589

Gnomad4 OTH

AF:

0.0224

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.0295

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.9

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over