rs13003334

chr2-218260198-T-A

Variant summary

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

The NM_001321950.2(GPBAR1):c.-46+14T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,142 control chromosomes in the GnomAD database, including 18,016 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 (18012 hom., cov: 33)
  • Exomes 𝑓: 0.71 (4 hom.)
• Consequence: GPBAR1 NM_001321950.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPBAR1	NM_001321950.2	c.-46+14T>A		intron_variant
GPBAR1	XM_011510743.1	c.-667+14T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPBAR1	ENST00000479077.5	c.-46+14T>A		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68796 AN: 152010 Hom.: 17989 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.714 AC: 10 AN: 14 Hom.: 4 Cov.: 0 AF XY: 0.800 AC XY: 8 AN XY: 10

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.453 AC: 68845 AN: 152128 Hom.: 18012 Cov.: 33 AF XY: 0.459 AC XY: 34112 AN XY: 74364

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.449

Alfa AF: 0.499 Hom.: 2574

Bravo AF: 0.423

Asia WGS AF: 0.606 AC: 2109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.47
Dann	Benign	0.81

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: rs13003334; hg19: chr2-219124921;