11-18934179-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001393578.1(MRGPRX1):c.606T>C(p.Ile202=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,608,094 control chromosomes in the GnomAD database, including 122 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 (113 hom.)
• Consequence: MRGPRX1 NM_001393578.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.04

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 11-18934179-A-G is Benign according to our data. Variant chr11-18934179-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2641671.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.04 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRGPRX1	NM_001393578.1	c.606T>C	p.Ile202=	synonymous_variant	2/2	ENST00000526914.2
MRGPRX1	NM_147199.4	c.606T>C	p.Ile202=	synonymous_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRGPRX1	ENST00000526914.2	c.606T>C	p.Ile202=	synonymous_variant	2/2	3	NM_001393578.1	P1
MRGPRX1	ENST00000302797.4	c.606T>C	p.Ile202=	synonymous_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.00223 AC: 337 AN: 151296 Hom.: 9 Cov.: 35

Gnomad AFR AF: 0.000752

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00518

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00297

Gnomad OTH AF: 0.00483

GnomAD3 exomes AF: 0.00105 AC: 262 AN: 250408 Hom.: 10 AF XY: 0.000923 AC XY: 125 AN XY: 135366

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.000232

Gnomad NFE exome AF: 0.00131

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00169 AC: 2467 AN: 1456680 Hom.: 113 Cov.: 32 AF XY: 0.00171 AC XY: 1240 AN XY: 724706

Gnomad4 AFR exome AF: 0.000359

Gnomad4 AMR exome AF: 0.00355

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000930

Gnomad4 FIN exome AF: 0.000281

Gnomad4 NFE exome AF: 0.00194

Gnomad4 OTH exome AF: 0.00191

GnomAD4 genome AF: 0.00223 AC: 337 AN: 151414 Hom.: 9 Cov.: 35 AF XY: 0.00222 AC XY: 164 AN XY: 73980

Gnomad4 AFR AF: 0.000750

Gnomad4 AMR AF: 0.00517

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000284

Gnomad4 NFE AF: 0.00297

Gnomad4 OTH AF: 0.00478

Alfa AF: 0.00194 Hom.: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

MRGPRX1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.83
Dann	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs188512916; hg19: chr11-18955726;