10-25417303-T-G

Variant names:

• chr10-25417303-T-G
• rs956088
• NM_020752.3:c.1335+4830T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020752.3(GPR158):​c.1335+4830T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 152,142 control chromosomes in the GnomAD database, including 52,784 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 0.82 (52784 hom., cov: 31)
• Consequence: GPR158 NM_020752.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR158	NM_020752.3	c.1335+4830T>G		intron_variant	Intron 4 of 10	ENST00000376351.4	NP_065803.2
GPR158	XR_930512.4	n.1755+4830T>G		intron_variant	Intron 4 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR158	ENST00000376351.4	c.1335+4830T>G		intron_variant	Intron 4 of 10	1	NM_020752.3	ENSP00000365529.3
GPR158	ENST00000650135.1	c.1098+4830T>G		intron_variant	Intron 5 of 11			ENSP00000498176.1

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125287 AN: 152024 Hom.: 52725 Cov.: 31

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.818

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

GnomAD4 genome AF: 0.824 AC: 125408 AN: 152142 Hom.: 52784 Cov.: 31 AF XY: 0.809 AC XY: 60159 AN XY: 74352

African (AFR) AF: 0.887 AC: 36853 AN: 41536

American (AMR) AF: 0.674 AC: 10298 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2781 AN: 3466

East Asian (EAS) AF: 0.343 AC: 1765 AN: 5150

South Asian (SAS) AF: 0.796 AC: 3842 AN: 4824

European-Finnish (FIN) AF: 0.735 AC: 7773 AN: 10572

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.873 AC: 59334 AN: 68004

Other (OTH) AF: 0.820 AC: 1729 AN: 2108

Alfa AF: 0.850 Hom.: 89794

Bravo AF: 0.818

Asia WGS AF: 0.601 AC: 2093 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.79
PhyloP100		-0.34
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: rs956088; hg19: chr10-25706232;