Variant chr2-218262955-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_170699.3(GPBAR1):c.231G>C(p.Gln77His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GPBAR1
NM_170699.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.772

Variant links:

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]

GPBAR1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09338865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPBAR1	NM_170699.3 link	c.231G>C	p.Gln77His	missense_variant	2/2	ENST00000519574.2	NP_733800.1	Q8TDU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GPBAR1	ENST00000519574.2 link	c.231G>C	p.Gln77His	missense_variant	2/2	1	NM_170699.3	ENSP00000430202.1	Q8TDU6
GPBAR1	ENST00000479077.5 link	c.231G>C	p.Gln77His	missense_variant	2/2	2		ENSP00000430698.1	Q8TDU6
GPBAR1	ENST00000521462.1 link	c.231G>C	p.Gln77His	missense_variant	2/2	2		ENSP00000428824.1	Q8TDU6
GPBAR1	ENST00000522678.5 link	c.231G>C	p.Gln77His	missense_variant	2/2	2		ENSP00000430886.1	Q8TDU6

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Oct 06, 2024

The c.231G>C (p.Q77H) alteration is located in exon 2 (coding exon 1) of the GPBAR1 gene. This alteration results from a G to C substitution at nucleotide position 231, causing the glutamine (Q) at amino acid position 77 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

9.1

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

T;T;T;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.62

.;.;.;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.093

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.60

N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.52

N;N;N;N

REVEL

Benign

0.063

Sift

Benign

0.18

T;T;T;T

Sift4G

Benign

0.076

T;T;T;T

Polyphen

0.0040

B;B;B;B

Vest4

0.25

MutPred

0.46

Gain of catalytic residue at Q77 (P = 0.1002);Gain of catalytic residue at Q77 (P = 0.1002);Gain of catalytic residue at Q77 (P = 0.1002);Gain of catalytic residue at Q77 (P = 0.1002);

MVP

0.55

MPC

0.042

ClinPred

0.12

GERP RS

3.3

Varity_R

0.091

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over