11-18934983-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393578.1(MRGPRX1):c.-25-174G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 669,714 control chromosomes in the GnomAD database, including 38,209 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (8450 hom., cov: 36)
  • Exomes 𝑓: 0.37 (29759 hom.)
• Consequence: MRGPRX1 NM_001393578.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRGPRX1	NM_001393578.1	c.-25-174G>A		intron_variant		ENST00000526914.2
MRGPRX1	NM_147199.4	c.-199G>A		5_prime_UTR_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRGPRX1	ENST00000526914.2	c.-25-174G>A		intron_variant		3	NM_001393578.1	P1
MRGPRX1	ENST00000302797.4	c.-199G>A		5_prime_UTR_variant	1/1			P1
	ENST00000528646.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.345 AC: 51358 AN: 148848 Hom.: 8447 Cov.: 36

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.371 AC: 193086 AN: 520748 Hom.: 29759 Cov.: 7 AF XY: 0.373 AC XY: 99054 AN XY: 265914

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.258

Gnomad4 ASJ exome AF: 0.332

Gnomad4 EAS exome AF: 0.307

Gnomad4 SAS exome AF: 0.377

Gnomad4 FIN exome AF: 0.521

Gnomad4 NFE exome AF: 0.371

Gnomad4 OTH exome AF: 0.366

GnomAD4 genome AF: 0.345 AC: 51409 AN: 148966 Hom.: 8450 Cov.: 36 AF XY: 0.352 AC XY: 25578 AN XY: 72696

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.344

Alfa AF: 0.378 Hom.: 1118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.2
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3858489; hg19: chr11-18956530; COSMIC: COSV57106192; COSMIC: COSV57106192;