chr2-218262686-C-A

Variant names:

• chr2-218262686-C-A
• rs57621524
• NM_170699.3:c.-39C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_170699.3(GPBAR1):​c.-39C>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 0.000000738 in 1,354,634 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: 7.4e-7 (0 hom.)
• Consequence: GPBAR1 NM_170699.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPBAR1	NM_170699.3	c.-39C>A		5_prime_UTR_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.-39C>A		5_prime_UTR_variant	Exon 2 of 2	1	NM_170699.3	ENSP00000430202.1
GPBAR1	ENST00000479077.5	c.-39C>A		5_prime_UTR_variant	Exon 2 of 2	2		ENSP00000430698.1
GPBAR1	ENST00000521462.1	c.-39C>A		5_prime_UTR_variant	Exon 2 of 2	2		ENSP00000428824.1
GPBAR1	ENST00000522678.5	c.-39C>A		5_prime_UTR_variant	Exon 2 of 2	2		ENSP00000430886.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1354634 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 662976

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31046

American (AMR) AF: 0.00 AC: 0 AN: 33430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21200

East Asian (EAS) AF: 0.00 AC: 0 AN: 37304

South Asian (SAS) AF: 0.00 AC: 0 AN: 71578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5132

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1062796

Other (OTH) AF: 0.0000178 AC: 1 AN: 56190

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.54
DANN	Benign	0.75
PhyloP100		-1.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs57621524; hg19: chr2-219127409;