11-57352573-A-G

Variant names:

• chr11-57352573-A-G
• rs3781902
• NM_002559.5:c.842+1675A>G

Variant summary

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

The NM_002559.5(P2RX3):​c.842+1675A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,052 control chromosomes in the GnomAD database, including 19,162 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 0.47 (19162 hom., cov: 32)
• Consequence: P2RX3 NM_002559.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 6 publications found

Genes affected

P2RX3 (HGNC:8534): (purinergic receptor P2X 3) This gene encodes a member of the P2X purinergic receptor (purinoceptor) gene family which includes seven members (P2RX1 - P2RX7). P2X purinoceptors are a family of cation-permeable, ligand-gated ion channels that open in response to the binding of extracellular adenosine 5'-triphosphate (ATP). The encoded protein is a subunit of the trimeric P2X3 receptor ion channel which is expressed by sensory or autonomic neurons. A deficiency of the orthologous protein in mice is associated with reduced pain-related behavior and urinary bladder hyporeflexia. [provided by RefSeq, Aug 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002559.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX3	NM_002559.5	MANE Select	c.842+1675A>G		intron	N/A	NP_002550.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX3	ENST00000263314.3	TSL:1 MANE Select	c.842+1675A>G		intron	N/A	ENSP00000263314.2

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71395 AN: 151934 Hom.: 19150 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.470 AC: 71440 AN: 152052 Hom.: 19162 Cov.: 32 AF XY: 0.481 AC XY: 35749 AN XY: 74316

African (AFR) AF: 0.199 AC: 8261 AN: 41478

American (AMR) AF: 0.634 AC: 9675 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2016 AN: 3472

East Asian (EAS) AF: 0.691 AC: 3574 AN: 5170

South Asian (SAS) AF: 0.675 AC: 3255 AN: 4822

European-Finnish (FIN) AF: 0.615 AC: 6505 AN: 10572

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36454 AN: 67958

Other (OTH) AF: 0.495 AC: 1044 AN: 2108

Alfa AF: 0.522 Hom.: 92344

Bravo AF: 0.459

Asia WGS AF: 0.668 AC: 2321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		-0.081
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: rs3781902; hg19: chr11-57120047;