Variant chr2-218262745-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_170699.3(GPBAR1):c.21C>G(p.Gly7=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,598,814 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00099 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 11 hom. )

Consequence

GPBAR1
NM_170699.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.351

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 2-218262745-C-G is Benign according to our data. Variant chr2-218262745-C-G is described in ClinVar as [Benign]. Clinvar id is 727294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.351 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPBAR1	NM_170699.3 linkuse as main transcript	c.21C>G	p.Gly7=	synonymous_variant	2/2	ENST00000519574.2	NP_733800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GPBAR1	ENST00000519574.2 linkuse as main transcript	c.21C>G	p.Gly7=	synonymous_variant	2/2	1	NM_170699.3	ENSP00000430202	P1
GPBAR1	ENST00000479077.5 linkuse as main transcript	c.21C>G	p.Gly7=	synonymous_variant	2/2	2		ENSP00000430698	P1
GPBAR1	ENST00000521462.1 linkuse as main transcript	c.21C>G	p.Gly7=	synonymous_variant	2/2	2		ENSP00000428824	P1
GPBAR1	ENST00000522678.5 linkuse as main transcript	c.21C>G	p.Gly7=	synonymous_variant	2/2	2		ENSP00000430886	P1

Frequencies

GnomAD3 genomes

AF:

0.000986

AC:

150

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00191

AC:

450

AN:

235114

Hom.:

AF XY:

0.00227

AC XY:

291

AN XY:

128318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000980

Gnomad ASJ exome

AF:

0.00237

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00989

Gnomad FIN exome

AF:

0.000159

Gnomad NFE exome

AF:

0.000825

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

AF:

0.00120

AC:

1736

AN:

1446572

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

1034

AN XY:

717568

show subpopulations

Gnomad4 AFR exome

AF:

0.000181

Gnomad4 AMR exome

AF:

0.000955

Gnomad4 ASJ exome

AF:

0.00228

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0104

Gnomad4 FIN exome

AF:

0.000177

Gnomad4 NFE exome

AF:

0.000523

Gnomad4 OTH exome

AF:

0.00176

GnomAD4 genome

AF:

0.000985

AC:

150

AN:

152242

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.000959

Hom.:

Bravo

AF:

0.000744

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	GPBAR1: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.81

DANN

Benign

0.56

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over