NM_170699.3:c.189C>A

Variant names:

• chr2-218262913-C-A
• NM_170699.3:c.189C>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_170699.3(GPBAR1):​c.189C>A​(p.Leu63Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,436 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPBAR1 NM_170699.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.942

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=0.942 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPBAR1	NM_170699.3	c.189C>A	p.Leu63Leu	synonymous_variant	Exon 2 of 2	ENST00000519574.2	NP_733800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPBAR1	ENST00000519574.2	c.189C>A	p.Leu63Leu	synonymous_variant	Exon 2 of 2	1	NM_170699.3	ENSP00000430202.1
GPBAR1	ENST00000479077.5	c.189C>A	p.Leu63Leu	synonymous_variant	Exon 2 of 2	2		ENSP00000430698.1
GPBAR1	ENST00000521462.1	c.189C>A	p.Leu63Leu	synonymous_variant	Exon 2 of 2	2		ENSP00000428824.1
GPBAR1	ENST00000522678.5	c.189C>A	p.Leu63Leu	synonymous_variant	Exon 2 of 2	2		ENSP00000430886.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461436 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726996

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.3
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-219127636;