rs57621524

Positions:

• chr2-218262686-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.-39C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00481 in 1,506,832 control chromosomes in the GnomAD database, including 245 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 0.023 (111 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (134 hom.)
• Consequence: GPBAR1 NM_170699.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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 = 0.0762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPBAR1	NM_170699.3	c.-39C>T		5_prime_UTR_premature_start_codon_gain_variant	2/2	ENST00000519574.2	NP_733800.1
GPBAR1	NM_170699.3	c.-39C>T		5_prime_UTR_variant	2/2	ENST00000519574.2	NP_733800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPBAR1	ENST00000519574	c.-39C>T		5_prime_UTR_premature_start_codon_gain_variant	2/2	1	NM_170699.3	ENSP00000430202.1
GPBAR1	ENST00000519574	c.-39C>T		5_prime_UTR_variant	2/2	1	NM_170699.3	ENSP00000430202.1

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3507 AN: 152116 Hom.: 110 Cov.: 32

Gnomad AFR AF: 0.0784

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00968

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: 0.000559

Gnomad OTH AF: 0.0220

GnomAD3 exomes AF: 0.00656 AC: 963 AN: 146828 Hom.: 26 AF XY: 0.00532 AC XY: 419 AN XY: 78708

Gnomad AFR exome AF: 0.0780

Gnomad AMR exome AF: 0.00405

Gnomad ASJ exome AF: 0.00470

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000266

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000572

Gnomad OTH exome AF: 0.00450

GnomAD4 exome AF: 0.00275 AC: 3727 AN: 1354598 Hom.: 134 Cov.: 30 AF XY: 0.00244 AC XY: 1618 AN XY: 662960

Gnomad4 AFR exome AF: 0.0861

Gnomad4 AMR exome AF: 0.00452

Gnomad4 ASJ exome AF: 0.00557

Gnomad4 EAS exome AF: 0.0000268

Gnomad4 SAS exome AF: 0.000238

Gnomad4 FIN exome AF: 0.0000556

Gnomad4 NFE exome AF: 0.000334

Gnomad4 OTH exome AF: 0.00683

GnomAD4 genome AF: 0.0231 AC: 3518 AN: 152234 Hom.: 111 Cov.: 32 AF XY: 0.0222 AC XY: 1654 AN XY: 74428

Gnomad4 AFR AF: 0.0785

Gnomad4 AMR AF: 0.00967

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.000559

Gnomad4 OTH AF: 0.0218

Alfa AF: 0.0137 Hom.: 20

Bravo AF: 0.0271

Asia WGS AF: 0.00549 AC: 20 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	3.3
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs57621524; hg19: chr2-219127409;