11-57352573-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX3	NM_002559.5	c.842+1675A>G		intron_variant		ENST00000263314.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX3	ENST00000263314.3	c.842+1675A>G		intron_variant		1	NM_002559.5	P1

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

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.495

Alfa AF: 0.537 Hom.: 46132

Bravo AF: 0.459

Asia WGS AF: 0.668 AC: 2321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	12
Dann	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs3781902; hg19: chr11-57120047;