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GeneBe

11-18934118-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001393578.1(MRGPRX1):c.667C>T(p.Leu223=) 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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.572 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 58 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MRGPRX1NM_001393578.1 linkuse as main transcriptc.667C>T p.Leu223= synonymous_variant 2/2 ENST00000526914.2
MRGPRX1NM_147199.4 linkuse as main transcriptc.667C>T p.Leu223= synonymous_variant 1/1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MRGPRX1ENST00000526914.2 linkuse as main transcriptc.667C>T p.Leu223= synonymous_variant 2/23 NM_001393578.1 P1
MRGPRX1ENST00000302797.4 linkuse as main transcriptc.667C>T p.Leu223= synonymous_variant 1/1 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00976
AC:
1477
AN:
151360
Hom.:
58
Cov.:
35
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.:
26
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.:
59
Cov.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00977
AC:
1480
AN:
151478
Hom.:
59
Cov.:
35
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.:
10
Bravo
AF:
0.0108
EpiCase
AF:
0.0000546
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeOct 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.

Other links and lift over

dbSNP: rs112335646; hg19: chr11-18955665; API