Variant 11-18174062-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_054032.3(MRGPRX4):c.806C>T(p.Pro269Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00847 in 1,614,172 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0087 ( 63 hom. )

Consequence

MRGPRX4
NM_054032.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.22

Variant links:

Genes affected

MRGPRX4 (HGNC:17617): (MAS related GPR family member X4) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to act upstream of or within chemosensory behavior and hematopoietic progenitor cell differentiation. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MRGPRX4 links:

ENSG00000255470 (HGNC:):

ENSG00000255470 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05511862).

BP6

Variant 11-18174062-C-T is Benign according to our data. Variant chr11-18174062-C-T is described in ClinVar as [Benign]. Clinvar id is 774894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRX4	NM_054032.3 linkuse as main transcript	c.806C>T	p.Pro269Leu	missense_variant	1/1	ENST00000314254.3	NP_473373.2	Q96LA9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRGPRX4	ENST00000314254.3 linkuse as main transcript	c.806C>T	p.Pro269Leu	missense_variant	1/1	6	NM_054032.3	ENSP00000314042.3		Q96LA9
ENSG00000255470	ENST00000527671.1 linkuse as main transcript	n.601+14833G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00577

AC:

878

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00396

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00588

AC:

1480

AN:

251488

Hom.:

AF XY:

0.00603

AC XY:

819

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00222

Gnomad FIN exome

AF:

0.00536

Gnomad NFE exome

AF:

0.0102

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00875

AC:

12788

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00861

AC XY:

6263

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00248

Gnomad4 FIN exome

AF:

0.00513

Gnomad4 NFE exome

AF:

0.0105

Gnomad4 OTH exome

AF:

0.00692

GnomAD4 genome

AF:

0.00577

AC:

878

AN:

152280

Hom.:

Cov.:

AF XY:

0.00537

AC XY:

400

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00249

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.00396

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00913

Hom.:

Bravo

AF:

0.00498

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.0100

AC:

ExAC

AF:

0.00637

AC:

774

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00829

EpiControl

AF:

0.00776

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.055

MetaSVM

Pathogenic

0.88

MutationAssessor

Pathogenic

3.7

PrimateAI

Benign

0.30

PROVEAN

Pathogenic

-9.8

REVEL

Pathogenic

0.79

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.67

MVP

0.96

MPC

0.68

ClinPred

0.081

GERP RS

2.9

Varity_R

0.87

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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