rs56192869

Positions:

• chr2-218262694-G-A

Variant summary

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

The NM_170699.3(GPBAR1):​c.-31G>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 0.00517 in 1,520,630 control chromosomes in the GnomAD database, including 297 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 0.025 (138 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (159 hom.)
• Consequence: GPBAR1 NM_170699.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.458

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPBAR1	NM_170699.3	c.-31G>A		5_prime_UTR_variant	2/2	ENST00000519574.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPBAR1	ENST00000519574.2	c.-31G>A		5_prime_UTR_variant	2/2	1	NM_170699.3	P1
GPBAR1	ENST00000479077.5	c.-31G>A		5_prime_UTR_variant	2/2	2		P1
GPBAR1	ENST00000521462.1	c.-31G>A		5_prime_UTR_variant	2/2	2		P1
GPBAR1	ENST00000522678.5	c.-31G>A		5_prime_UTR_variant	2/2	2		P1

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3829 AN: 151980 Hom.: 138 Cov.: 32

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0226

GnomAD3 exomes AF: 0.00705 AC: 1163 AN: 165018 Hom.: 44 AF XY: 0.00563 AC XY: 503 AN XY: 89346

Gnomad AFR exome AF: 0.0853

Gnomad AMR exome AF: 0.00423

Gnomad ASJ exome AF: 0.00496

Gnomad EAS exome AF: 0.0000676

Gnomad SAS exome AF: 0.000172

Gnomad FIN exome AF: 0.000121

Gnomad NFE exome AF: 0.000607

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00294 AC: 4024 AN: 1368532 Hom.: 159 Cov.: 31 AF XY: 0.00262 AC XY: 1761 AN XY: 671276

Gnomad4 AFR exome AF: 0.0932

Gnomad4 AMR exome AF: 0.00475

Gnomad4 ASJ exome AF: 0.00558

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000231

Gnomad4 FIN exome AF: 0.000105

Gnomad4 NFE exome AF: 0.000339

Gnomad4 OTH exome AF: 0.00718

GnomAD4 genome AF: 0.0252 AC: 3840 AN: 152098 Hom.: 138 Cov.: 32 AF XY: 0.0241 AC XY: 1793 AN XY: 74352

Gnomad4 AFR AF: 0.0858

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.000589

Gnomad4 OTH AF: 0.0224

Alfa AF: 0.0127 Hom.: 24

Bravo AF: 0.0295

Asia WGS AF: 0.00606 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs56192869; hg19: chr2-219127417;