2-218261086-C-T

Variant summary

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

The NM_170699.3(GPBAR1):c.-176C>T 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 152,188 control chromosomes in the GnomAD database, including 17,945 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 (17923 hom., cov: 33)
  • Exomes 𝑓: 0.62 (22 hom.)
• Consequence: GPBAR1 NM_170699.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567

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_170699.3	c.-176C>T		5_prime_UTR_variant	1/2	ENST00000519574.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPBAR1	ENST00000519574.2	c.-176C>T		5_prime_UTR_variant	1/2	1	NM_170699.3	P1
GPBAR1	ENST00000521462.1	c.-289C>T		5_prime_UTR_variant	1/2	2		P1
GPBAR1	ENST00000522678.5	c.-797C>T		5_prime_UTR_variant	1/2	2		P1
GPBAR1	ENST00000479077.5	c.-46+902C>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68258 AN: 151966 Hom.: 17900 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.618 AC: 63 AN: 102 Hom.: 22 Cov.: 0 AF XY: 0.618 AC XY: 47 AN XY: 76

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.628

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.449 AC: 68304 AN: 152086 Hom.: 17923 Cov.: 33 AF XY: 0.455 AC XY: 33865 AN XY: 74352

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.446

Alfa AF: 0.528 Hom.: 21136

Bravo AF: 0.419

Asia WGS AF: 0.605 AC: 2105 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	6.7
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs11554825; hg19: chr2-219125809;