chr2-218262852-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_170699.3(GPBAR1):c.128G>A(p.Arg43His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_170699.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GPBAR1 | NM_170699.3 | c.128G>A | p.Arg43His | missense_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.128G>A | p.Arg43His | missense_variant | 2/2 | 1 | NM_170699.3 | ENSP00000430202 | P1 | |
GPBAR1 | ENST00000479077.5 | c.128G>A | p.Arg43His | missense_variant | 2/2 | 2 | ENSP00000430698 | P1 | ||
GPBAR1 | ENST00000521462.1 | c.128G>A | p.Arg43His | missense_variant | 2/2 | 2 | ENSP00000428824 | P1 | ||
GPBAR1 | ENST00000522678.5 | c.128G>A | p.Arg43His | missense_variant | 2/2 | 2 | ENSP00000430886 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000202 AC: 5AN: 247508Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134466
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461324Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 726952
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74312
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2023 | The c.128G>A (p.R43H) alteration is located in exon 2 (coding exon 1) of the GPBAR1 gene. This alteration results from a G to A substitution at nucleotide position 128, causing the arginine (R) at amino acid position 43 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
GPBAR1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 18, 2022 | The GPBAR1 c.128G>A variant is predicted to result in the amino acid substitution p.Arg43His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.015% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-219127575-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at