chr11-18934187-T-C

Variant names:

• chr11-18934187-T-C
• rs200061528
• NM_001393578.1:c.598A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001393578.1(MRGPRX1):​c.598A>G​(p.Ile200Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,607,696 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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 (119 hom.)
• Consequence: MRGPRX1 NM_001393578.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.89
• Publications: 7 publications found

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]

ENSG00000255244 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0058268607).
• BP6: Variant 11-18934187-T-C is Benign according to our data. Variant chr11-18934187-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2641672.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.598A>G	p.Ile200Val	missense	Exon 2 of 2	NP_001380507.1	Q96LB2
	MRGPRX1	NM_147199.4		c.598A>G	p.Ile200Val	missense	Exon 1 of 1	NP_671732.3	Q96LB2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRGPRX1	ENST00000526914.2	TSL:3 MANE Select	c.598A>G	p.Ile200Val	missense	Exon 2 of 2	ENSP00000499076.2	Q96LB2
	MRGPRX1	ENST00000302797.4	TSL:6	c.598A>G	p.Ile200Val	missense	Exon 1 of 1	ENSP00000305766.3	Q96LB2
	ENSG00000255244	ENST00000836338.1		n.374-5118T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00223 AC: 337 AN: 150882 Hom.: 9 Cov.: 35

Gnomad AFR AF: 0.000754

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00519

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000286

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00297

Gnomad OTH AF: 0.00485

GnomAD2 exomes AF: 0.000847 AC: 212 AN: 250362 AF XY: 0.000776

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.00199

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000232

Gnomad NFE exome AF: 0.00103

Gnomad OTH exome AF: 0.00197

GnomAD4 exome AF: 0.00173 AC: 2516 AN: 1456694 Hom.: 119 Cov.: 32 AF XY: 0.00176 AC XY: 1274 AN XY: 724738

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

African (AFR) AF: 0.000359 AC: 12 AN: 33446

American (AMR) AF: 0.00366 AC: 162 AN: 44256

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26098

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39654

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86036

European-Finnish (FIN) AF: 0.000300 AC: 16 AN: 53348

Middle Eastern (MID) AF: 0.00209 AC: 12 AN: 5752

European-Non Finnish (NFE) AF: 0.00196 AC: 2176 AN: 1107866

Other (OTH) AF: 0.00199 AC: 120 AN: 60238

⚠️ 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.

GnomAD4 genome AF: 0.00223 AC: 337 AN: 151002 Hom.: 9 Cov.: 35 AF XY: 0.00222 AC XY: 164 AN XY: 73734

African (AFR) AF: 0.000752 AC: 31 AN: 41246

American (AMR) AF: 0.00519 AC: 78 AN: 15042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5094

South Asian (SAS) AF: 0.00 AC: 0 AN: 4716

European-Finnish (FIN) AF: 0.000286 AC: 3 AN: 10498

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.00297 AC: 201 AN: 67658

Other (OTH) AF: 0.00480 AC: 10 AN: 2084

Alfa AF: 0.00161 Hom.: 1

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.000350 AC: 3

ExAC AF: 0.000990 AC: 120

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.0010
DANN	Benign	0.14
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-2.7
Eigen_PC	Benign	-2.8
FATHMM_MKL	Benign	0.0079	N
LIST_S2	Benign	0.065	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.1	N
PhyloP100		-5.9
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.35	N
REVEL	Benign	0.064
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.019
MVP		0.10
MPC		0.032
ClinPred		0.012	T
GERP RS		-4.6
Varity_R		0.020
gMVP		0.029
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs200061528; hg19: chr11-18955734; COSMIC: COSV106100727; COSMIC: COSV106100727;