Variant 11-18934118-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001393578.1(MRGPRX1):c.667C>T(p.Leu223Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 1,610,844 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0098 ( 59 hom., cov: 35)

Exomes 𝑓: 0.0011 ( 59 hom. )

Consequence

MRGPRX1
NM_001393578.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.572

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 11-18934118-G-A is Benign according to our data. Variant chr11-18934118-G-A is described in ClinVar as [Benign]. Clinvar id is 718088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.572 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00977 (1480/151478) while in subpopulation AFR AF= 0.0339 (1401/41316). AF 95% confidence interval is 0.0324. There are 59 homozygotes in gnomad4. There are 687 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 59 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRX1	NM_001393578.1 linkuse as main transcript	c.667C>T	p.Leu223Leu	synonymous_variant	2/2	ENST00000526914.2	NP_001380507.1
MRGPRX1	NM_147199.4 linkuse as main transcript	c.667C>T	p.Leu223Leu	synonymous_variant	1/1		NP_671732.3	Q96LB2W8W3P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRGPRX1	ENST00000526914.2 linkuse as main transcript	c.667C>T	p.Leu223Leu	synonymous_variant	2/2	3	NM_001393578.1	ENSP00000499076.2		Q96LB2A0A494C1K4
MRGPRX1	ENST00000302797.4 linkuse as main transcript	c.667C>T	p.Leu223Leu	synonymous_variant	1/1	6		ENSP00000305766.3		Q96LB2

Frequencies

GnomAD3 genomes

AF:

0.00976

AC:

1477

AN:

151360

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00311

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000192

Gnomad OTH

AF:

0.00772

GnomAD3 exomes

AF:

0.00254

AC:

636

AN:

250704

Hom.:

AF XY:

0.00173

AC XY:

235

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.0350

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.00106

AC:

1547

AN:

1459366

Hom.:

Cov.:

AF XY:

0.000921

AC XY:

669

AN XY:

725994

show subpopulations

Gnomad4 AFR exome

AF:

0.0372

Gnomad4 AMR exome

AF:

0.00149

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000865

Gnomad4 OTH exome

AF:

0.00206

GnomAD4 genome

AF:

0.00977

AC:

1480

AN:

151478

Hom.:

Cov.:

AF XY:

0.00928

AC XY:

687

AN XY:

74030

show subpopulations

Gnomad4 AFR

AF:

0.0339

Gnomad4 AMR

AF:

0.00311

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000192

Gnomad4 OTH

AF:

0.00764

Alfa

AF:

0.00465

Hom.:

Bravo

AF:

0.0108

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000178

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	Oct 19, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.0

DANN

Benign

0.88

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