rs147288525

Variant names:

• chr11-18934206-C-A
• rs147288525
• NM_001393578.1:c.579G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-18934206-C-A
• chr11-18934206-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.684
• Publications: 3 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: 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

Sel.	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.: 9 Cov.: 35

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

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.: 37 AF XY: 0.00180 AC XY: 1305 AN XY: 724788

⚠️ 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: 0.00368 AC: 163 AN: 44264

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26102

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

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86038

European-Finnish (FIN) AF: 0.000281 AC: 15 AN: 53336

Middle Eastern (MID) AF: 0.00139 AC: 8 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.

GnomAD4 genome AF: 0.00223 AC: 336 AN: 150970 Hom.: 9 Cov.: 35 AF XY: 0.00222 AC XY: 164 AN XY: 73782

African (AFR) AF: 0.000752 AC: 31 AN: 41242

American (AMR) AF: 0.00526 AC: 79 AN: 15028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5086

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

European-Finnish (FIN) AF: 0.000190 AC: 2 AN: 10542

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

European-Non Finnish (NFE) AF: 0.00296 AC: 200 AN: 67610

Other (OTH) AF: 0.00478 AC: 10 AN: 2090

Alfa AF: 0.00180 Hom.: 4

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
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.9
DANN	Benign	0.79
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs147288525; hg19: chr11-18955753;