2-218262963-G-T

Variant names:

• chr2-218262963-G-T
• rs201747442
• NM_170699.3:c.239G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_170699.3(GPBAR1):​c.239G>T​(p.Arg80Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPBAR1 NM_170699.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.930

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]

ACMG classification

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=0.09329265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPBAR1	NM_170699.3	c.239G>T	p.Arg80Leu	missense_variant	Exon 2 of 2	ENST00000519574.2	NP_733800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPBAR1	ENST00000519574.2	c.239G>T	p.Arg80Leu	missense_variant	Exon 2 of 2	1	NM_170699.3	ENSP00000430202.1
GPBAR1	ENST00000479077.5	c.239G>T	p.Arg80Leu	missense_variant	Exon 2 of 2	2		ENSP00000430698.1
GPBAR1	ENST00000521462.1	c.239G>T	p.Arg80Leu	missense_variant	Exon 2 of 2	2		ENSP00000428824.1
GPBAR1	ENST00000522678.5	c.239G>T	p.Arg80Leu	missense_variant	Exon 2 of 2	2		ENSP00000430886.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248940 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135064

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.6
DANN	Benign	0.70
DEOGEN2	Benign	0.031	T;T;T;T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.59	.;.;.;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.093	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.94	N;N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.97	N;N;N;N
REVEL	Benign	0.074
Sift	Benign	0.75	T;T;T;T
Sift4G	Benign	0.33	T;T;T;T
Polyphen		0.0010	B;B;B;B
Vest4		0.14
MutPred		0.70		Loss of catalytic residue at R80 (P = 0.0898);Loss of catalytic residue at R80 (P = 0.0898);Loss of catalytic residue at R80 (P = 0.0898);Loss of catalytic residue at R80 (P = 0.0898);
MVP		0.16
MPC		0.051
ClinPred		0.044	T
GERP RS		2.1
Varity_R		0.10
gMVP		0.45

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

Other links and lift over

dbSNP: rs201747442; hg19: chr2-219127686;