rs56192869

Variant names:

• chr2-218262694-G-A
• rs56192869
• NM_170699.3:c.-31G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-218262694-G-A
• chr2-218262694-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0834 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.-31G>A		5_prime_UTR	Exon 2 of 2	NP_733800.1	Q8TDU6
	GPBAR1	NM_001077191.2		c.-31G>A		5_prime_UTR	Exon 2 of 2	NP_001070659.1	Q8TDU6
	GPBAR1	NM_001077194.2		c.-31G>A		5_prime_UTR	Exon 2 of 2	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.-31G>A		5_prime_UTR	Exon 2 of 2	ENSP00000430202.1	Q8TDU6
	GPBAR1	ENST00000479077.5	TSL:2	c.-31G>A		5_prime_UTR	Exon 2 of 2	ENSP00000430698.1	Q8TDU6
	GPBAR1	ENST00000521462.1	TSL:2	c.-31G>A		5_prime_UTR	Exon 2 of 2	ENSP00000428824.1	Q8TDU6

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

GnomAD2 exomes AF: 0.00705 AC: 1163 AN: 165018 AF XY: 0.00563

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 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

African (AFR) AF: 0.0932 AC: 2917 AN: 31306

American (AMR) AF: 0.00475 AC: 166 AN: 34924

Ashkenazi Jewish (ASJ) AF: 0.00558 AC: 121 AN: 21668

East Asian (EAS) AF: 0.00 AC: 0 AN: 37942

South Asian (SAS) AF: 0.000231 AC: 17 AN: 73702

European-Finnish (FIN) AF: 0.000105 AC: 4 AN: 38196

Middle Eastern (MID) AF: 0.00569 AC: 30 AN: 5268

European-Non Finnish (NFE) AF: 0.000339 AC: 362 AN: 1068842

Other (OTH) AF: 0.00718 AC: 407 AN: 56684

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

African (AFR) AF: 0.0858 AC: 3558 AN: 41484

American (AMR) AF: 0.0109 AC: 167 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10592

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000589 AC: 40 AN: 67966

Other (OTH) AF: 0.0224 AC: 47 AN: 2102

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.59
PhyloP100		0.46
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs56192869; hg19: chr2-219127417;