Genetic Variant MRGPRX1:p.Gly193Gly (chr11-18934206-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001393578.1(MRGPRX1):c.579G>T(p.Gly193Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,607,712 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts 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 ( 120 hom. )

Consequence

MRGPRX1
NM_001393578.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.684

Publications

3 publications found

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:

ENSG00000255244 (HGNC:):

ENSG00000255244 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 11-18934206-C-A is Benign according to our data. Variant chr11-18934206-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2641673.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393578.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRGPRX1	NM_001393578.1	MANE Select	c.579G>T	p.Gly193Gly	synonymous	Exon 2 of 2	NP_001380507.1	Q96LB2
	MRGPRX1	NM_147199.4		c.579G>T	p.Gly193Gly	synonymous	Exon 1 of 1	NP_671732.3	Q96LB2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRGPRX1	ENST00000526914.2	TSL:3 MANE Select	c.579G>T	p.Gly193Gly	synonymous	Exon 2 of 2	ENSP00000499076.2	Q96LB2
MRGPRX1	ENST00000302797.4	TSL:6	c.579G>T	p.Gly193Gly	synonymous	Exon 1 of 1	ENSP00000305766.3	Q96LB2
ENSG00000255244	ENST00000836338.1		n.374-5099C>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00223

AC:

336

AN:

150852

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000754

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00526

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00296

Gnomad OTH

AF:

0.00484

GnomAD2 exomes

AF:

0.000576

AC:

144

AN:

250194

AF XY:

0.000458

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00149

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000707

Gnomad OTH exome

AF:

0.000983

GnomAD4 exome

AF:

0.00175

AC:

2548

AN:

1456742

Hom.:

120

Cov.:

AF XY:

0.00180

AC XY:

1305

AN XY:

724788

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000359

AC:

AN:

33446

American (AMR)

AF:

0.00368

AC:

163

AN:

44264

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26102

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39654

South Asian (SAS)

AF:

0.000139

AC:

AN:

86038

European-Finnish (FIN)

AF:

0.000281

AC:

AN:

53336

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00200

AC:

2213

AN:

1107902

Other (OTH)

AF:

0.00199

AC:

120

AN:

60248

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.354

Heterozygous variant carriers

131

262

392

523

654

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00223

AC:

336

AN:

150970

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

164

AN XY:

73782

show subpopulations

African (AFR)

AF:

0.000752

AC:

AN:

41242

American (AMR)

AF:

0.00526

AC:

AN:

15028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5086

South Asian (SAS)

AF:

0.00

AC:

AN:

4716

European-Finnish (FIN)

AF:

0.000190

AC:

AN:

10542

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00296

AC:

200

AN:

67610

Other (OTH)

AF:

0.00478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00180

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.9

(source)

DANN

Benign

0.79

PhyloP100

-0.68

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over