11-18934621-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001393578.1(MRGPRX1):c.164G>T(p.Arg55Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,610,266 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0080 (28 hom., cov: 35)
  • Exomes 𝑓: 0.00093 (58 hom.)
• Consequence: MRGPRX1 NM_001393578.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.10

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033153892).
• BP6: Variant 11-18934621-C-A is Benign according to our data. Variant chr11-18934621-C-A is described in ClinVar as [Benign]. Clinvar id is 789791.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00797 (1207/151434) while in subpopulation AFR AF= 0.028 (1157/41286). AF 95% confidence interval is 0.0267. There are 28 homozygotes in gnomad4. There are 551 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRGPRX1	NM_001393578.1	c.164G>T	p.Arg55Leu	missense_variant	2/2	ENST00000526914.2
MRGPRX1	NM_147199.4	c.164G>T	p.Arg55Leu	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRGPRX1	ENST00000526914.2	c.164G>T	p.Arg55Leu	missense_variant	2/2	3	NM_001393578.1	P1
MRGPRX1	ENST00000302797.4	c.164G>T	p.Arg55Leu	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.00797 AC: 1206 AN: 151316 Hom.: 28 Cov.: 35

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00225

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000737

Gnomad OTH AF: 0.00531

GnomAD3 exomes AF: 0.00235 AC: 589 AN: 250196 Hom.: 20 AF XY: 0.00161 AC XY: 218 AN XY: 135262

Gnomad AFR exome AF: 0.0327

Gnomad AMR exome AF: 0.00126

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000882

Gnomad OTH exome AF: 0.000822

GnomAD4 exome AF: 0.000933 AC: 1361 AN: 1458832 Hom.: 58 Cov.: 46 AF XY: 0.000801 AC XY: 581 AN XY: 725708

Gnomad4 AFR exome AF: 0.0344

Gnomad4 AMR exome AF: 0.00127

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000369

Gnomad4 OTH exome AF: 0.00173

GnomAD4 genome AF: 0.00797 AC: 1207 AN: 151434 Hom.: 28 Cov.: 35 AF XY: 0.00745 AC XY: 551 AN XY: 73990

Gnomad4 AFR AF: 0.0280

Gnomad4 AMR AF: 0.00225

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000738

Gnomad4 OTH AF: 0.00526

Alfa AF: 0.000709 Hom.: 1

ESP6500AA AF: 0.0330 AC: 145

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.00281 AC: 341

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	18
Dann	Uncertain	0.99
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.031	N
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.5	H
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.21	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.050
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.021	D
Polyphen		0.99	D
Vest4		0.21
MVP		0.42
MPC		0.16
ClinPred		0.086	T
GERP RS		0.39
Varity_R		0.32
gMVP		0.18

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

Other links and lift over

dbSNP: rs55954376; hg19: chr11-18956168;