10-25501915-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.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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GPR158	NM_020752.3	c.1404+35196A>G		intron_variant		ENST00000376351.4
GPR158	XM_017016452.3	c.-157+35196A>G		intron_variant
GPR158	XR_930512.4	n.1824+35196A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR158	ENST00000376351.4	c.1404+35196A>G		intron_variant		1	NM_020752.3	P2
GPR158	ENST00000650135.1	c.1167+35196A>G		intron_variant				A2

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

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.532

Alfa AF: 0.550 Hom.: 4661

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

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: rs1536836; hg19: chr10-25790844;