chr11-18934179-A-G

Variant names:

• chr11-18934179-A-G
• rs188512916
• NM_001393578.1:c.606T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001393578.1(MRGPRX1):​c.606T>C​(p.Ile202Ile) 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
• Publications: 2 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 -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 VariationId 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 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.606T>C	p.Ile202Ile	synonymous	Exon 2 of 2	NP_001380507.1	Q96LB2
	MRGPRX1	NM_147199.4		c.606T>C	p.Ile202Ile	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.606T>C	p.Ile202Ile	synonymous	Exon 2 of 2	ENSP00000499076.2	Q96LB2
	MRGPRX1	ENST00000302797.4	TSL:6	c.606T>C	p.Ile202Ile	synonymous	Exon 1 of 1	ENSP00000305766.3	Q96LB2
	ENSG00000255244	ENST00000836338.1		n.374-5126A>G		intron	N/A

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

GnomAD2 exomes AF: 0.00105 AC: 262 AN: 250408 AF XY: 0.000923

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 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

⚠️ 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: 33448

American (AMR) AF: 0.00355 AC: 157 AN: 44246

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

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

South Asian (SAS) AF: 0.0000930 AC: 8 AN: 86038

European-Finnish (FIN) AF: 0.000281 AC: 15 AN: 53352

Middle Eastern (MID) AF: 0.00174 AC: 10 AN: 5756

European-Non Finnish (NFE) AF: 0.00194 AC: 2145 AN: 1107850

Other (OTH) AF: 0.00191 AC: 115 AN: 60234

⚠️ 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: 151414 Hom.: 9 Cov.: 35 AF XY: 0.00222 AC XY: 164 AN XY: 73980

African (AFR) AF: 0.000750 AC: 31 AN: 41360

American (AMR) AF: 0.00517 AC: 78 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4750

European-Finnish (FIN) AF: 0.000284 AC: 3 AN: 10558

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

European-Non Finnish (NFE) AF: 0.00297 AC: 201 AN: 67780

Other (OTH) AF: 0.00478 AC: 10 AN: 2092

Alfa AF: 0.00194 Hom.: 2

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	-1.0
CADD	Benign	0.83
DANN	Benign	0.31
PhyloP100		-5.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs188512916; hg19: chr11-18955726;