10-25501915-A-G

Variant names:

• chr10-25501915-A-G
• rs1536836
• NM_020752.3:c.1404+35196A>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.1404+35196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 151,860 control chromosomes in the GnomAD database, including 26,424 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 0.58 (26424 hom., cov: 31)
• Consequence: GPR158 NM_020752.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR158	NM_020752.3	c.1404+35196A>G		intron_variant	Intron 5 of 10	ENST00000376351.4	NP_065803.2
GPR158	XM_017016452.3	c.-157+35196A>G		intron_variant	Intron 2 of 7		XP_016871941.1
GPR158	XR_930512.4	n.1824+35196A>G		intron_variant	Intron 5 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR158	ENST00000376351.4	c.1404+35196A>G		intron_variant	Intron 5 of 10	1	NM_020752.3	ENSP00000365529.3
GPR158	ENST00000650135.1	c.1167+35196A>G		intron_variant	Intron 6 of 11			ENSP00000498176.1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88437 AN: 151742 Hom.: 26381 Cov.: 31

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.583 AC: 88530 AN: 151860 Hom.: 26424 Cov.: 31 AF XY: 0.585 AC XY: 43393 AN XY: 74218

African (AFR) AF: 0.713 AC: 29549 AN: 41430

American (AMR) AF: 0.501 AC: 7651 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1482 AN: 3466

East Asian (EAS) AF: 0.704 AC: 3617 AN: 5140

South Asian (SAS) AF: 0.522 AC: 2505 AN: 4802

European-Finnish (FIN) AF: 0.584 AC: 6155 AN: 10540

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.530 AC: 35987 AN: 67910

Other (OTH) AF: 0.532 AC: 1123 AN: 2112

Alfa AF: 0.554 Hom.: 4857

Bravo AF: 0.583

Asia WGS AF: 0.626 AC: 2178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.34
PhyloP100		-0.73
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: rs1536836; hg19: chr10-25790844;