2-218263783-C-T

Variant names:

• chr2-218263783-C-T
• rs2292549
• NM_170699.3:c.*66C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_170699.3(GPBAR1):​c.*66C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 1,591,806 control chromosomes in the GnomAD database, including 710,341 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.81 (54079 hom., cov: 33)
  • Exomes 𝑓: 0.95 (656262 hom.)
• Consequence: GPBAR1 NM_170699.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPBAR1	NM_170699.3	c.*66C>T		3_prime_UTR_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.*66C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_170699.3	ENSP00000430202.1
GPBAR1	ENST00000479077.5	c.*66C>T		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000430698.1
GPBAR1	ENST00000521462.1	c.*66C>T		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000428824.1
GPBAR1	ENST00000522678.5	c.*66C>T		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000430886.1

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122823 AN: 152108 Hom.: 54066 Cov.: 33

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.974

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.963

Gnomad OTH AF: 0.836

GnomAD4 exome AF: 0.951 AC: 1368598 AN: 1439580 Hom.: 656262 Cov.: 26 AF XY: 0.953 AC XY: 683686 AN XY: 717530

Gnomad4 AFR exome AF: 0.393

Gnomad4 AMR exome AF: 0.941

Gnomad4 ASJ exome AF: 0.913

Gnomad4 EAS exome AF: 0.989

Gnomad4 SAS exome AF: 0.974

Gnomad4 FIN exome AF: 0.977

Gnomad4 NFE exome AF: 0.966

Gnomad4 OTH exome AF: 0.928

GnomAD4 genome AF: 0.807 AC: 122866 AN: 152226 Hom.: 54079 Cov.: 33 AF XY: 0.811 AC XY: 60380 AN XY: 74424

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.907

Gnomad4 ASJ AF: 0.906

Gnomad4 EAS AF: 0.991

Gnomad4 SAS AF: 0.974

Gnomad4 FIN AF: 0.974

Gnomad4 NFE AF: 0.963

Gnomad4 OTH AF: 0.839

Alfa AF: 0.932 Hom.: 125277

Bravo AF: 0.784

Asia WGS AF: 0.935 AC: 3251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.056
DANN	Benign	0.75

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: rs2292549; hg19: chr2-219128506;