2-218262941-GGGCTG-CA

Variant names:

• chr2-218262941-GGGCTG-CA
• rs1559489631
• NM_170699.3:c.217_222delGGGCTGinsCA

Variant summary

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

The NM_170699.3(GPBAR1):​c.217_222delGGGCTGinsCA​(p.Gly73HisfsTer42) variant causes a frameshift, missense 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, missense
• Clinical Significance: Uncertain significance criteria provided, single submitter 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 rank	MANE	Protein	UniProt
GPBAR1	NM_170699.3	c.217_222delGGGCTGinsCA	p.Gly73HisfsTer42	frameshift_variant, missense_variant	Exon 2 of 2	ENST00000519574.2	NP_733800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPBAR1	ENST00000519574.2	c.217_222delGGGCTGinsCA	p.Gly73HisfsTer42	frameshift_variant, missense_variant	Exon 2 of 2	1	NM_170699.3	ENSP00000430202.1
GPBAR1	ENST00000479077.5	c.217_222delGGGCTGinsCA	p.Gly73HisfsTer42	frameshift_variant, missense_variant	Exon 2 of 2	2		ENSP00000430698.1
GPBAR1	ENST00000521462.1	c.217_222delGGGCTGinsCA	p.Gly73HisfsTer42	frameshift_variant, missense_variant	Exon 2 of 2	2		ENSP00000428824.1
GPBAR1	ENST00000522678.5	c.217_222delGGGCTGinsCA	p.Gly73HisfsTer42	frameshift_variant, missense_variant	Exon 2 of 2	2		ENSP00000430886.1

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, single submitter

Submissions by phenotype

GPBAR1-related disorder Uncertain:1

Feb 19, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

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. -

not provided Uncertain:1

May 25, 2018

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;