10-25244607-T-C

Variant names:

• chr10-25244607-T-C
• rs1416995
• NM_020752.3:c.1008+23450T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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]

ENSG00000274242 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020752.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR158	NM_020752.3	MANE Select	c.1008+23450T>C		intron	N/A	NP_065803.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR158	ENST00000376351.4	TSL:1 MANE Select	c.1008+23450T>C		intron	N/A	ENSP00000365529.3
	ENSG00000274242	ENST00000613843.1	TSL:6	n.248A>G		non_coding_transcript_exon	Exon 1 of 2
	GPR158	ENST00000650135.1		c.771+23450T>C		intron	N/A	ENSP00000498176.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0556 AC: 1 AN: 18

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.437 AC: 18071 AN: 41350

American (AMR) AF: 0.195 AC: 2972 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3470

East Asian (EAS) AF: 0.306 AC: 1574 AN: 5150

South Asian (SAS) AF: 0.204 AC: 983 AN: 4808

European-Finnish (FIN) AF: 0.0592 AC: 627 AN: 10594

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0826 AC: 5615 AN: 67990

Other (OTH) AF: 0.175 AC: 369 AN: 2110

Alfa AF: 0.116 Hom.: 2822

Bravo AF: 0.220

Asia WGS AF: 0.300 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.80
PhyloP100		-1.6
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: rs1416995; hg19: chr10-25533536;