10-25302224-A-G

Position:

• chr10-25302224-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020752.3(GPR158):​c.1008+81067A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 147,632 control chromosomes in the GnomAD database, including 5,160 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 0.20 (5160 hom., cov: 26)
• Consequence: GPR158 NM_020752.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.465

Genes affected

GPR158 (HGNC:23689): (G protein-coupled receptor 158) Predicted to enable G protein-coupled receptor activity. Predicted to act upstream of or within G protein-coupled receptor signaling pathway and protein localization to plasma membrane. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR158 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR158	NM_020752.3	c.1008+81067A>G		intron_variant		ENST00000376351.4	NP_065803.2
GPR158	XR_930512.4	n.1428+81067A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR158	ENST00000376351.4	c.1008+81067A>G		intron_variant		1	NM_020752.3	ENSP00000365529.3
GPR158	ENST00000650135.1	c.771+81067A>G		intron_variant				ENSP00000498176.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30099 AN: 147564 Hom.: 5145 Cov.: 26

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0877

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0579

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.0925

Gnomad OTH AF: 0.183

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.204 AC: 30164 AN: 147632 Hom.: 5160 Cov.: 26 AF XY: 0.202 AC XY: 14509 AN XY: 71770

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.0877

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.0579

Gnomad4 NFE AF: 0.0925

Gnomad4 OTH AF: 0.188

Alfa AF: 0.0392 Hom.: 26

Bravo AF: 0.217

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.9
DANN	Benign	0.41

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: rs59132240; hg19: chr10-25591153;