NM_054030.4:c.-25-1318T>C

Variant names:

• chr11-19057745-A-G
• rs7116312
• NM_054030.4:c.-25-1318T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_054030.4(MRGPRX2):​c.-25-1318T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,022 control chromosomes in the GnomAD database, including 9,034 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 0.33 (9034 hom., cov: 33)
• Consequence: MRGPRX2 NM_054030.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 4 publications found

Genes affected

MRGPRX2 (HGNC:17983): (MAS related GPR family member X2) Enables G protein-coupled receptor activity and neuropeptide binding activity. Involved in mast cell degranulation and positive regulation of cytokinesis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRGPRX2	NM_054030.4	c.-25-1318T>C		intron_variant	Intron 1 of 1	ENST00000329773.3	NP_473371.1
MRGPRX2	NM_001303615.2	c.-25-1318T>C		intron_variant	Intron 2 of 2		NP_001290544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRGPRX2	ENST00000329773.3	c.-25-1318T>C		intron_variant	Intron 1 of 1	1	NM_054030.4	ENSP00000333800.2

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50110 AN: 151902 Hom.: 9016 Cov.: 33

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.315

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.330 AC: 50163 AN: 152022 Hom.: 9034 Cov.: 33 AF XY: 0.325 AC XY: 24126 AN XY: 74334

African (AFR) AF: 0.488 AC: 20222 AN: 41400

American (AMR) AF: 0.325 AC: 4968 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1071 AN: 3470

East Asian (EAS) AF: 0.256 AC: 1324 AN: 5176

South Asian (SAS) AF: 0.186 AC: 897 AN: 4822

European-Finnish (FIN) AF: 0.208 AC: 2206 AN: 10582

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18645 AN: 67974

Other (OTH) AF: 0.310 AC: 653 AN: 2104

Alfa AF: 0.283 Hom.: 11493

Bravo AF: 0.345

Asia WGS AF: 0.205 AC: 713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.7
DANN	Benign	0.59
PhyloP100		0.047
Mutation Taster		=100/0	polymorphism (auto)

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: rs7116312; hg19: chr11-19079292;