Variant 11-18934222-C-A 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.563G>T(p.Cys188Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,610,420 control chromosomes in the GnomAD database, including 4 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 0.00011 ( 0 hom., cov: 35)

Exomes 𝑓: 0.00012 ( 4 hom. )

Consequence

MRGPRX1
NM_001393578.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.598

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=0.013083398).

BP6

Variant 11-18934222-C-A is Benign according to our data. Variant chr11-18934222-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2346538.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRX1	NM_001393578.1 link	c.563G>T	p.Cys188Phe	missense_variant	2/2	ENST00000526914.2	NP_001380507.1
MRGPRX1	NM_147199.4 link	c.563G>T	p.Cys188Phe	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.563G>T	p.Cys188Phe	missense_variant	2/2	3	NM_001393578.1	ENSP00000499076.2		Q96LB2A0A494C1K4
MRGPRX1	ENST00000302797.4 link	c.563G>T	p.Cys188Phe	missense_variant	1/1	6		ENSP00000305766.3		Q96LB2

Frequencies

GnomAD3 genomes

AF:

0.000106

AC:

AN:

151004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000285

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000192

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000148

AC:

AN:

250810

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000602

Gnomad NFE exome

AF:

0.000202

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000121

AC:

176

AN:

1459416

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

726022

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000544

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.0000995

GnomAD4 genome

AF:

0.000106

AC:

AN:

151004

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

73710

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000285

Gnomad4 NFE

AF:

0.000192

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000103

Hom.:

Bravo

AF:

0.0000831

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.038

DANN

Benign

0.74

DEOGEN2

Benign

0.0037

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0053

LIST_S2

Benign

0.28

M_CAP

Benign

0.0026

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.78

PrimateAI

Benign

0.25

PROVEAN

Benign

4.7

REVEL

Benign

0.027

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.10

MVP

0.12

MPC

0.046

ClinPred

0.046

GERP RS

-0.71

Varity_R

0.074

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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