Variant rs202233050 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_170699.3(GPBAR1):c.12C>G(p.Asn4Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,130 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GPBAR1
NM_170699.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

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 4 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity GPBAR_HUMAN

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 link	c.12C>G	p.Asn4Lys	missense_variant	Exon 2 of 2	ENST00000519574.2	NP_733800.1	Q8TDU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPBAR1	ENST00000519574.2 link	c.12C>G	p.Asn4Lys	missense_variant	Exon 2 of 2	1	NM_170699.3	ENSP00000430202.1	Q8TDU6
GPBAR1	ENST00000479077.5 link	c.12C>G	p.Asn4Lys	missense_variant	Exon 2 of 2	2		ENSP00000430698.1	Q8TDU6
GPBAR1	ENST00000521462.1 link	c.12C>G	p.Asn4Lys	missense_variant	Exon 2 of 2	2		ENSP00000428824.1	Q8TDU6
GPBAR1	ENST00000522678.5 link	c.12C>G	p.Asn4Lys	missense_variant	Exon 2 of 2	2		ENSP00000430886.1	Q8TDU6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.95e-7

AC:

AN:

1439130

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712918

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;T;T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.52

.;.;.;T

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.48

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.1

M;M;M;M

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Benign

0.083

Sift

Uncertain

0.012

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.56

MutPred

0.16

Gain of ubiquitination at N4 (P = 0.0014);Gain of ubiquitination at N4 (P = 0.0014);Gain of ubiquitination at N4 (P = 0.0014);Gain of ubiquitination at N4 (P = 0.0014);

MVP

0.33

MPC

0.32

ClinPred

0.66

GERP RS

2.8

Varity_R

0.11

gMVP

0.50

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over