10-25244607-T-C

Position:

• chr10-25244607-T-C

Variant summary

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

The NM_020752.3(GPR158):​c.1008+23450T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 151,980 control chromosomes in the GnomAD database, including 4,955 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 (4954 hom., cov: 32)
  • Exomes 𝑓: 0.18 (1 hom.)
• Consequence: GPR158 NM_020752.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

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]

ENSG00000274242 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR158	NM_020752.3	c.1008+23450T>C		intron_variant		ENST00000376351.4	NP_065803.2
GPR158	XR_930512.4	n.1428+23450T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR158	ENST00000376351.4	c.1008+23450T>C		intron_variant		1	NM_020752.3	ENSP00000365529.3
GPR158	ENST00000650135.1	c.771+23450T>C		intron_variant				ENSP00000498176.1
ENSG00000274242	ENST00000613843.1	n.248A>G		non_coding_transcript_exon_variant	1/2	6

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30555 AN: 151840 Hom.: 4908 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.0592

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0826

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.182 AC: 4 AN: 22 Hom.: 1 Cov.: 0 AF XY: 0.0714 AC XY: 1 AN XY: 14

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.0556

GnomAD4 genome AF: 0.202 AC: 30666 AN: 151958 Hom.: 4954 Cov.: 32 AF XY: 0.202 AC XY: 15034 AN XY: 74306

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.0592

Gnomad4 NFE AF: 0.0826

Gnomad4 OTH AF: 0.175

Alfa AF: 0.105 Hom.: 1696

Bravo AF: 0.220

Asia WGS AF: 0.300 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.80

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: rs1416995; hg19: chr10-25533536;