chr2-218259499-G-A

Position:

• chr2-218259499-G-A

Variant summary

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

The NM_001321950.2(GPBAR1):​c.-731G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,350 control chromosomes in the GnomAD database, including 17,952 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 0.45 (17905 hom., cov: 32)
  • Exomes 𝑓: 0.58 (47 hom.)
• Consequence: GPBAR1 NM_001321950.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.79

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPBAR1	NM_001321950.2	c.-731G>A		5_prime_UTR_variant	1/2
GPBAR1	XM_011510743.1	c.-1352G>A		5_prime_UTR_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPBAR1	ENST00000479077.5	c.-731G>A		5_prime_UTR_variant	1/2	2		P1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68229 AN: 151966 Hom.: 17882 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.576 AC: 152 AN: 264 Hom.: 47 Cov.: 0 AF XY: 0.544 AC XY: 98 AN XY: 180

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.400

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.625

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.708

Gnomad4 NFE exome AF: 0.596

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.449 AC: 68276 AN: 152086 Hom.: 17905 Cov.: 32 AF XY: 0.455 AC XY: 33848 AN XY: 74334

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.446

Alfa AF: 0.528 Hom.: 21054

Bravo AF: 0.418

Asia WGS AF: 0.605 AC: 2104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.023
DANN	Benign	0.78

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: rs3731859; hg19: chr2-219124222;