2-218262941-GGGCTG-CA
Position:
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
NM_170699.3 frameshift
Scores
Not classified
Clinical Significance
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GPBAR1 | NM_170699.3 | c.217_222delinsCA | p.Gly73HisfsTer42 | frameshift_variant | 2/2 | ENST00000519574.2 | NP_733800.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GPBAR1 | ENST00000519574.2 | c.217_222delinsCA | p.Gly73HisfsTer42 | frameshift_variant | 2/2 | 1 | NM_170699.3 | ENSP00000430202 | P1 | |
GPBAR1 | ENST00000479077.5 | c.217_222delinsCA | p.Gly73HisfsTer42 | frameshift_variant | 2/2 | 2 | ENSP00000430698 | P1 | ||
GPBAR1 | ENST00000521462.1 | c.217_222delinsCA | p.Gly73HisfsTer42 | frameshift_variant | 2/2 | 2 | ENSP00000428824 | P1 | ||
GPBAR1 | ENST00000522678.5 | c.217_222delinsCA | p.Gly73HisfsTer42 | frameshift_variant | 2/2 | 2 | ENSP00000430886 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
GPBAR1-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 25, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at