chr2-218262012-C-T

Position:

• chr2-218262012-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.-45-668C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 153,974 control chromosomes in the GnomAD database, including 55,098 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 0.81 (54241 hom., cov: 31)
  • Exomes 𝑓: 0.95 (857 hom.)
• Consequence: GPBAR1 NM_170699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPBAR1	NM_170699.3	c.-45-668C>T		intron_variant		ENST00000519574.2	NP_733800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPBAR1	ENST00000519574.2	c.-45-668C>T		intron_variant		1	NM_170699.3	ENSP00000430202.1
GPBAR1	ENST00000479077.5	c.-45-668C>T		intron_variant		2		ENSP00000430698.1
GPBAR1	ENST00000521462.1	c.-158-555C>T		intron_variant		2		ENSP00000428824.1
GPBAR1	ENST00000522678.5	c.-666-47C>T		intron_variant		2		ENSP00000430886.1

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123227 AN: 151984 Hom.: 54228 Cov.: 31

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.974

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.963

Gnomad OTH AF: 0.840

GnomAD4 exome AF: 0.953 AC: 1784 AN: 1872 Hom.: 857 Cov.: 0 AF XY: 0.957 AC XY: 1299 AN XY: 1358

Gnomad4 AFR exome AF: 0.361

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.944

Gnomad4 SAS exome AF: 0.964

Gnomad4 FIN exome AF: 0.979

Gnomad4 NFE exome AF: 0.968

Gnomad4 OTH exome AF: 0.932

GnomAD4 genome AF: 0.810 AC: 123273 AN: 152102 Hom.: 54241 Cov.: 31 AF XY: 0.814 AC XY: 60556 AN XY: 74368

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.908

Gnomad4 ASJ AF: 0.906

Gnomad4 EAS AF: 0.991

Gnomad4 SAS AF: 0.975

Gnomad4 FIN AF: 0.974

Gnomad4 NFE AF: 0.962

Gnomad4 OTH AF: 0.842

Alfa AF: 0.849 Hom.: 7804

Bravo AF: 0.788

Asia WGS AF: 0.936 AC: 3253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.63
DANN	Benign	0.64

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: rs1567869; hg19: chr2-219126735;