2-218263783-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170699.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPBAR1	NM_170699.3	MANE Select	c.*66C>T		3_prime_UTR	Exon 2 of 2	NP_733800.1
	GPBAR1	NM_001077191.2		c.*66C>T		3_prime_UTR	Exon 2 of 2	NP_001070659.1
	GPBAR1	NM_001077194.2		c.*66C>T		3_prime_UTR	Exon 2 of 2	NP_001070662.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPBAR1	ENST00000519574.2	TSL:1 MANE Select	c.*66C>T		3_prime_UTR	Exon 2 of 2	ENSP00000430202.1
	GPBAR1	ENST00000479077.5	TSL:2	c.*66C>T		3_prime_UTR	Exon 2 of 2	ENSP00000430698.1
	GPBAR1	ENST00000521462.1	TSL:2	c.*66C>T		3_prime_UTR	Exon 2 of 2	ENSP00000428824.1

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

African (AFR) AF: 0.393 AC: 12967 AN: 32988

American (AMR) AF: 0.941 AC: 42036 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.913 AC: 23736 AN: 25994

East Asian (EAS) AF: 0.989 AC: 39146 AN: 39562

South Asian (SAS) AF: 0.974 AC: 83595 AN: 85844

European-Finnish (FIN) AF: 0.977 AC: 51071 AN: 52288

Middle Eastern (MID) AF: 0.901 AC: 5159 AN: 5724

European-Non Finnish (NFE) AF: 0.966 AC: 1055539 AN: 1092854

Other (OTH) AF: 0.928 AC: 55349 AN: 59670

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

African (AFR) AF: 0.417 AC: 17280 AN: 41484

American (AMR) AF: 0.907 AC: 13885 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3145 AN: 3472

East Asian (EAS) AF: 0.991 AC: 5141 AN: 5186

South Asian (SAS) AF: 0.974 AC: 4700 AN: 4824

European-Finnish (FIN) AF: 0.974 AC: 10341 AN: 10622

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.963 AC: 65467 AN: 68016

Other (OTH) AF: 0.839 AC: 1771 AN: 2112

Alfa AF: 0.903 Hom.: 173874

Bravo AF: 0.784

Asia WGS AF: 0.935 AC: 3251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.056
DANN	Benign	0.75
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2292549; hg19: chr2-219128506;