rs1341204755

Variant names:

• chr2-218262836-G-A
• rs1341204755
• NM_170699.3:c.112G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-218262836-G-A
• chr2-218262836-G-C

Variant summary

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

The NM_170699.3(GPBAR1):​c.112G>A​(p.Gly38Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 8.11

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 2 ACMG points.

• 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	c.112G>A	p.Gly38Ser	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.112G>A	p.Gly38Ser	missense_variant	Exon 2 of 2	1	NM_170699.3	ENSP00000430202.1
GPBAR1	ENST00000479077.5	c.112G>A	p.Gly38Ser	missense_variant	Exon 2 of 2	2		ENSP00000430698.1
GPBAR1	ENST00000521462.1	c.112G>A	p.Gly38Ser	missense_variant	Exon 2 of 2	2		ENSP00000428824.1
GPBAR1	ENST00000522678.5	c.112G>A	p.Gly38Ser	missense_variant	Exon 2 of 2	2		ENSP00000430886.1

Frequencies

GnomAD3 genomes Cov.: 32

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	0.24
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;T;T;T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.76	.;.;.;T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.59	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;L;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.43	N;N;N;N
REVEL	Benign	0.087
Sift	Uncertain	0.019	D;D;D;D
Sift4G	Benign	0.072	T;T;T;T
Polyphen		0.94	P;P;P;P
Vest4		0.68
MutPred		0.39		Gain of glycosylation at G38 (P = 0.3339);Gain of glycosylation at G38 (P = 0.3339);Gain of glycosylation at G38 (P = 0.3339);Gain of glycosylation at G38 (P = 0.3339);
MVP		0.52
MPC		0.31
ClinPred		0.96	D
GERP RS		4.0
Varity_R		0.25
gMVP		0.57

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: rs1341204755; hg19: chr2-219127559;