2-218262745-C-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.351

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]

ACMG classification

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 GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPBAR1	NM_170699.3	c.21C>G	p.Gly7=	synonymous_variant	2/2	ENST00000519574.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPBAR1	ENST00000519574.2	c.21C>G	p.Gly7=	synonymous_variant	2/2	1	NM_170699.3	P1
GPBAR1	ENST00000479077.5	c.21C>G	p.Gly7=	synonymous_variant	2/2	2		P1
GPBAR1	ENST00000521462.1	c.21C>G	p.Gly7=	synonymous_variant	2/2	2		P1
GPBAR1	ENST00000522678.5	c.21C>G	p.Gly7=	synonymous_variant	2/2	2		P1

Frequencies

GnomAD3 genomes AF: 0.000986 AC: 150 AN: 152124 Hom.: 2 Cov.: 32

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.: 2 AF XY: 0.00227 AC XY: 291 AN XY: 128318

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.: 11 Cov.: 31 AF XY: 0.00144 AC XY: 1034 AN XY: 717568

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.: 2 Cov.: 32 AF XY: 0.00133 AC XY: 99 AN XY: 74432

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.: 0

Bravo AF: 0.000744

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	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

Other links and lift over

dbSNP: rs201145373; hg19: chr2-219127468;