Variant 10-25599251-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020752.3(GPR158):c.3625A>G(p.Ile1209Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,609,174 control chromosomes in the GnomAD database, including 188,620 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.58 ( 28959 hom., cov: 31)

Exomes 𝑓: 0.46 ( 159661 hom. )

Consequence

GPR158
NM_020752.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.874

Variant links:

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]

GPR158 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.771142E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GPR158	NM_020752.3 linkuse as main transcript	c.3625A>G	p.Ile1209Val	missense_variant	11/11	ENST00000376351.4
GPR158	XM_017016452.3 linkuse as main transcript	c.2065A>G	p.Ile689Val	missense_variant	8/8
GPR158	XR_930512.4 linkuse as main transcript	n.4045A>G		non_coding_transcript_exon_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GPR158	ENST00000376351.4 linkuse as main transcript	c.3625A>G	p.Ile1209Val	missense_variant	11/11	1	NM_020752.3	P2
GPR158	ENST00000490549.1 linkuse as main transcript	n.1812A>G		non_coding_transcript_exon_variant	3/3	1
GPR158	ENST00000650135.1 linkuse as main transcript	c.3388A>G	p.Ile1130Val	missense_variant	12/12			A2

Frequencies

GnomAD3 genomes

AF:

0.581

AC:

88339

AN:

151930

Hom.:

28894

Cov.:

show subpopulations

Gnomad AFR

AF:

0.888

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.753

Gnomad SAS

AF:

0.519

Gnomad FIN

AF:

0.488

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.432

Gnomad OTH

AF:

0.514

GnomAD3 exomes

AF:

0.507

AC:

125842

AN:

248222

Hom.:

34295

AF XY:

0.494

AC XY:

66516

AN XY:

134522

show subpopulations

Gnomad AFR exome

AF:

0.896

Gnomad AMR exome

AF:

0.517

Gnomad ASJ exome

AF:

0.383

Gnomad EAS exome

AF:

0.769

Gnomad SAS exome

AF:

0.501

Gnomad FIN exome

AF:

0.491

Gnomad NFE exome

AF:

0.424

Gnomad OTH exome

AF:

0.461

GnomAD4 exome

AF:

0.458

AC:

667390

AN:

1457126

Hom.:

159661

Cov.:

AF XY:

0.456

AC XY:

330927

AN XY:

725078

show subpopulations

Gnomad4 AFR exome

AF:

0.904

Gnomad4 AMR exome

AF:

0.516

Gnomad4 ASJ exome

AF:

0.376

Gnomad4 EAS exome

AF:

0.734

Gnomad4 SAS exome

AF:

0.497

Gnomad4 FIN exome

AF:

0.493

Gnomad4 NFE exome

AF:

0.429

Gnomad4 OTH exome

AF:

0.484

GnomAD4 genome

AF:

0.582

AC:

88469

AN:

152048

Hom.:

28959

Cov.:

AF XY:

0.584

AC XY:

43403

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.889

Gnomad4 AMR

AF:

0.525

Gnomad4 ASJ

AF:

0.392

Gnomad4 EAS

AF:

0.753

Gnomad4 SAS

AF:

0.518

Gnomad4 FIN

AF:

0.488

Gnomad4 NFE

AF:

0.432

Gnomad4 OTH

AF:

0.515

Alfa

AF:

0.435

Hom.:

29404

Bravo

AF:

0.598

TwinsUK

AF:

0.424

AC:

1573

ALSPAC

AF:

0.421

AC:

1622

ESP6500AA

AF:

0.867

AC:

3819

ESP6500EA

AF:

0.424

AC:

3647

ExAC

AF:

0.514

AC:

62359

Asia WGS

AF:

0.648

AC:

2248

AN:

3478

EpiCase

AF:

0.404

EpiControl

AF:

0.398

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.4

DANN

Benign

0.16

DEOGEN2

Benign

0.0077

.;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.16

T;T

MetaRNN

Benign

7.8e-7

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.34

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

0.42

.;N

REVEL

Benign

0.15

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

.;T

Polyphen

0.0

.;B

Vest4

0.0060

MPC

0.079

ClinPred

0.0026

GERP RS

3.1

Varity_R

0.027

gMVP

0.053

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over