11-57340143-G-A

Variant names:

• chr11-57340143-G-A
• rs11603691
• NM_002559.5:c.119+1474G>A

Variant summary

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

The NM_002559.5(P2RX3):​c.119+1474G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 152,296 control chromosomes in the GnomAD database, including 539 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 0.073 (539 hom., cov: 32)
• Consequence: P2RX3 NM_002559.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX3	NM_002559.5	MANE Select	c.119+1474G>A		intron	N/A	NP_002550.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX3	ENST00000263314.3	TSL:1 MANE Select	c.119+1474G>A		intron	N/A	ENSP00000263314.2	P56373
	P2RX3	ENST00000946171.1		c.119+1474G>A		intron	N/A	ENSP00000616230.1
	P2RX3	ENST00000892409.1		c.119+1474G>A		intron	N/A	ENSP00000562468.1

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11146 AN: 152178 Hom.: 540 Cov.: 32

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0796

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.0445

Gnomad FIN AF: 0.0825

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0774

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

GnomAD4 genome AF: 0.0731 AC: 11140 AN: 152296 Hom.: 539 Cov.: 32 AF XY: 0.0715 AC XY: 5328 AN XY: 74486

African (AFR) AF: 0.0196 AC: 816 AN: 41576

American (AMR) AF: 0.0795 AC: 1216 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0896 AC: 311 AN: 3472

East Asian (EAS) AF: 0.0135 AC: 70 AN: 5186

South Asian (SAS) AF: 0.0443 AC: 214 AN: 4832

European-Finnish (FIN) AF: 0.0825 AC: 876 AN: 10612

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.108 AC: 7346 AN: 67996

Other (OTH) AF: 0.0762 AC: 161 AN: 2114

Alfa AF: 0.0428 Hom.: 47

Bravo AF: 0.0714

Asia WGS AF: 0.0330 AC: 117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.5
DANN	Benign	0.70
PhyloP100		-0.37
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: rs11603691; hg19: chr11-57107617;