2-218262012-C-T

Variant names:

• chr2-218262012-C-T
• rs1567869
• NM_170699.3:c.-45-668C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170699.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPBAR1	NM_170699.3	MANE Select	c.-45-668C>T		intron	N/A	NP_733800.1	Q8TDU6
	GPBAR1	NM_001077191.2		c.-666-47C>T		intron	N/A	NP_001070659.1	Q8TDU6
	GPBAR1	NM_001077194.2		c.-158-555C>T		intron	N/A	NP_001070662.1	Q8TDU6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPBAR1	ENST00000519574.2	TSL:1 MANE Select	c.-45-668C>T		intron	N/A	ENSP00000430202.1	Q8TDU6
	GPBAR1	ENST00000479077.5	TSL:2	c.-45-668C>T		intron	N/A	ENSP00000430698.1	Q8TDU6
	GPBAR1	ENST00000521462.1	TSL:2	c.-158-555C>T		intron	N/A	ENSP00000428824.1	Q8TDU6

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

African (AFR) AF: 0.361 AC: 13 AN: 36

American (AMR) AF: 1.00 AC: 28 AN: 28

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 4 AN: 4

East Asian (EAS) AF: 0.944 AC: 185 AN: 196

South Asian (SAS) AF: 0.964 AC: 27 AN: 28

European-Finnish (FIN) AF: 0.979 AC: 47 AN: 48

Middle Eastern (MID) AF: 1.00 AC: 6 AN: 6

European-Non Finnish (NFE) AF: 0.968 AC: 1405 AN: 1452

Other (OTH) AF: 0.932 AC: 69 AN: 74

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

African (AFR) AF: 0.428 AC: 17730 AN: 41420

American (AMR) AF: 0.908 AC: 13887 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3143 AN: 3470

East Asian (EAS) AF: 0.991 AC: 5123 AN: 5170

South Asian (SAS) AF: 0.975 AC: 4697 AN: 4818

European-Finnish (FIN) AF: 0.974 AC: 10335 AN: 10616

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.962 AC: 65444 AN: 67994

Other (OTH) AF: 0.842 AC: 1776 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.63
DANN	Benign	0.64
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1567869; hg19: chr2-219126735;