Genetic Variant MRGPRX1:c.-25-174G>A (chr11-18934983-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_147199.4(MRGPRX1):c.-199G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 669,714 control chromosomes in the GnomAD database, including 38,209 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 8450 hom., cov: 36)

Exomes 𝑓: 0.37 ( 29759 hom. )

Consequence

MRGPRX1
NM_147199.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.455

Publications

5 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147199.4. 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.-25-174G>A		intron	N/A	NP_001380507.1
	MRGPRX1	NM_147199.4		c.-199G>A		5_prime_UTR	Exon 1 of 1	NP_671732.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MRGPRX1	ENST00000526914.2	TSL:3 MANE Select	c.-25-174G>A	intron	N/A	ENSP00000499076.2
MRGPRX1	ENST00000302797.4	TSL:6	c.-199G>A	5_prime_UTR	Exon 1 of 1	ENSP00000305766.3
ENSG00000255244	ENST00000836338.1		n.374-4322C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

51358

AN:

148848

Hom.:

8447

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.415

Gnomad FIN

AF:

0.538

Gnomad MID

AF:

0.347

Gnomad NFE

AF:

0.392

Gnomad OTH

AF:

0.344

GnomAD4 exome

AF:

0.371

AC:

193086

AN:

520748

Hom.:

29759

Cov.:

AF XY:

0.373

AC XY:

99054

AN XY:

265914

show subpopulations

African (AFR)

AF:

0.238

AC:

3491

AN:

14644

American (AMR)

AF:

0.258

AC:

4282

AN:

16572

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

4249

AN:

12810

East Asian (EAS)

AF:

0.307

AC:

8764

AN:

28570

South Asian (SAS)

AF:

0.377

AC:

11782

AN:

31282

European-Finnish (FIN)

AF:

0.521

AC:

21114

AN:

40540

Middle Eastern (MID)

AF:

0.386

AC:

884

AN:

2288

European-Non Finnish (NFE)

AF:

0.371

AC:

128724

AN:

347310

Other (OTH)

AF:

0.366

AC:

9796

AN:

26732

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

4104

8208

12313

16417

20521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2206

4412

6618

8824

11030

<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:

0.345

AC:

51409

AN:

148966

Hom.:

8450

Cov.:

AF XY:

0.352

AC XY:

25578

AN XY:

72696

show subpopulations

African (AFR)

AF:

0.235

AC:

9575

AN:

40778

American (AMR)

AF:

0.297

AC:

4402

AN:

14802

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

1148

AN:

3404

East Asian (EAS)

AF:

0.315

AC:

1607

AN:

5104

South Asian (SAS)

AF:

0.415

AC:

1957

AN:

4714

European-Finnish (FIN)

AF:

0.538

AC:

5496

AN:

10218

Middle Eastern (MID)

AF:

0.356

AC:

104

AN:

292

European-Non Finnish (NFE)

AF:

0.393

AC:

26176

AN:

66688

Other (OTH)

AF:

0.344

AC:

707

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

1021

2042

3062

4083

5104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

520

1040

1560

2080

2600

<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:

0.378

Hom.:

1118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.2

(source)

DANN

Benign

0.48

PhyloP100

-0.46

PromoterAI

0.015

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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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