rs3858489

Variant names:

• chr11-18934983-C-A
• rs3858489
• NM_001393578.1:c.-25-174G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-18934983-C-A
• chr11-18934983-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_147199.4(MRGPRX1):​c.-199G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 532,194 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 36)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: MRGPRX1 NM_147199.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455
• Publications: 5 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147199.4. 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.-25-174G>T		intron	N/A	NP_001380507.1
	MRGPRX1	NM_147199.4		c.-199G>T		5_prime_UTR	Exon 1 of 1	NP_671732.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRGPRX1	ENST00000526914.2	TSL:3 MANE Select	c.-25-174G>T		intron	N/A	ENSP00000499076.2
	MRGPRX1	ENST00000302797.4	TSL:6	c.-199G>T		5_prime_UTR	Exon 1 of 1	ENSP00000305766.3
	ENSG00000255244	ENST00000836338.1		n.374-4322C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome AF: 0.00000188 AC: 1 AN: 532194 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 271620

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

African (AFR) AF: 0.00 AC: 0 AN: 14910

American (AMR) AF: 0.00 AC: 0 AN: 16896

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13000

East Asian (EAS) AF: 0.00 AC: 0 AN: 28842

South Asian (SAS) AF: 0.00 AC: 0 AN: 31848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2322

European-Non Finnish (NFE) AF: 0.00000281 AC: 1 AN: 355242

Other (OTH) AF: 0.00 AC: 0 AN: 27258

⚠️ 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 Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.43
PhyloP100		-0.46
PromoterAI		-0.024	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3858489; hg19: chr11-18956530;