2-218262941-GGGCTG-CA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_170699.3(GPBAR1):c.217_222delinsCA(p.Gly73HisfsTer42) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPBAR1 NM_170699.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 4.99

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPBAR1	NM_170699.3	c.217_222delinsCA	p.Gly73HisfsTer42	frameshift_variant	2/2	ENST00000519574.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPBAR1	ENST00000519574.2	c.217_222delinsCA	p.Gly73HisfsTer42	frameshift_variant	2/2	1	NM_170699.3	P1
GPBAR1	ENST00000479077.5	c.217_222delinsCA	p.Gly73HisfsTer42	frameshift_variant	2/2	2		P1
GPBAR1	ENST00000521462.1	c.217_222delinsCA	p.Gly73HisfsTer42	frameshift_variant	2/2	2		P1
GPBAR1	ENST00000522678.5	c.217_222delinsCA	p.Gly73HisfsTer42	frameshift_variant	2/2	2		P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 25, 2018

- -

GPBAR1-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 19, 2024

The GPBAR1 c.217_222delinsCA variant is predicted to result in a frameshift and premature protein termination (p.Gly73Hisfs*42). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. Loss of function is not an established mechanism for GPBAR1– associated disease. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1559489631; hg19: chr2-219127664;