Variant 11-18934187-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001393578.1(MRGPRX1):c.598A>G(p.Ile200Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,607,696 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 9 hom., cov: 35)

Exomes 𝑓: 0.0017 ( 119 hom. )

Consequence

MRGPRX1
NM_001393578.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.89

Variant links:

Genes affected

MRGPRX1 (HGNC:17962): (MAS related GPR family member X1) Enables transmembrane signaling receptor activity. Involved in cell surface receptor signaling pathway and response to chloroquine. Predicted to be located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

MRGPRX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058268607).

BP6

Variant 11-18934187-T-C is Benign according to our data. Variant chr11-18934187-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2641672.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-18934187-T-C is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRX1	NM_001393578.1 link	c.598A>G	p.Ile200Val	missense_variant	2/2	ENST00000526914.2	NP_001380507.1
MRGPRX1	NM_147199.4 link	c.598A>G	p.Ile200Val	missense_variant	1/1		NP_671732.3	Q96LB2W8W3P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRGPRX1	ENST00000526914.2 link	c.598A>G	p.Ile200Val	missense_variant	2/2	3	NM_001393578.1	ENSP00000499076.2		Q96LB2A0A494C1K4
MRGPRX1	ENST00000302797.4 link	c.598A>G	p.Ile200Val	missense_variant	1/1	6		ENSP00000305766.3		Q96LB2

Frequencies

GnomAD3 genomes

AF:

0.00223

AC:

337

AN:

150882

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000754

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00519

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000286

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00297

Gnomad OTH

AF:

0.00485

GnomAD3 exomes

AF:

0.000847

AC:

212

AN:

250362

Hom.:

AF XY:

0.000776

AC XY:

105

AN XY:

135354

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.00199

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.00173

AC:

2516

AN:

1456694

Hom.:

119

Cov.:

AF XY:

0.00176

AC XY:

1274

AN XY:

724738

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.00366

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00196

Gnomad4 OTH exome

AF:

0.00199

GnomAD4 genome

AF:

0.00223

AC:

337

AN:

151002

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

164

AN XY:

73734

show subpopulations

Gnomad4 AFR

AF:

0.000752

Gnomad4 AMR

AF:

0.00519

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000286

Gnomad4 NFE

AF:

0.00297

Gnomad4 OTH

AF:

0.00480

Alfa

AF:

0.00161

Hom.:

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000350

AC:

ExAC

AF:

0.000990

AC:

120

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

MRGPRX1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.0010

DANN

Benign

0.14

DEOGEN2

Benign

0.0029

Eigen

Benign

-2.7

Eigen_PC

Benign

-2.8

FATHMM_MKL

Benign

0.0079

LIST_S2

Benign

0.065

M_CAP

Benign

0.0024

MetaRNN

Benign

0.0058

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.1

PrimateAI

Benign

0.21

PROVEAN

Benign

0.35

REVEL

Benign

0.064

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.019

MVP

0.10

MPC

0.032

ClinPred

0.012

GERP RS

-4.6

Varity_R

0.020

gMVP

0.029

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over