2-218262819-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_170699.3(GPBAR1):āc.95A>Gā(p.Asn32Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000055 ( 0 hom. )
Consequence
GPBAR1
NM_170699.3 missense
NM_170699.3 missense
Scores
8
8
3
Clinical Significance
Conservation
PhyloP100: 4.87
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.914
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GPBAR1 | NM_170699.3 | c.95A>G | p.Asn32Ser | 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.95A>G | p.Asn32Ser | missense_variant | 2/2 | 1 | NM_170699.3 | ENSP00000430202 | P1 | |
GPBAR1 | ENST00000479077.5 | c.95A>G | p.Asn32Ser | missense_variant | 2/2 | 2 | ENSP00000430698 | P1 | ||
GPBAR1 | ENST00000521462.1 | c.95A>G | p.Asn32Ser | missense_variant | 2/2 | 2 | ENSP00000428824 | P1 | ||
GPBAR1 | ENST00000522678.5 | c.95A>G | p.Asn32Ser | missense_variant | 2/2 | 2 | ENSP00000430886 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000162 AC: 4AN: 247268Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134402
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461270Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726948
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
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2
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 27, 2024 | The c.95A>G (p.N32S) alteration is located in exon 2 (coding exon 1) of the GPBAR1 gene. This alteration results from a A to G substitution at nucleotide position 95, causing the asparagine (N) at amino acid position 32 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;D;D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;.;.;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
D;D;D;D
Vest4
MutPred
Gain of glycosylation at N32 (P = 0.1786);Gain of glycosylation at N32 (P = 0.1786);Gain of glycosylation at N32 (P = 0.1786);Gain of glycosylation at N32 (P = 0.1786);
MVP
MPC
0.28
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at