rs11603691

Positions:

• chr11-57340143-G-A
• chr11-57340143-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

P2RX3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX3	NM_002559.5	c.119+1474G>A		intron_variant		ENST00000263314.3	NP_002550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX3	ENST00000263314.3	c.119+1474G>A		intron_variant		1	NM_002559.5	ENSP00000263314.2
P2RX3	ENST00000533436.1	n.297-413G>A		intron_variant		3

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

Gnomad4 AFR AF: 0.0196

Gnomad4 AMR AF: 0.0795

Gnomad4 ASJ AF: 0.0896

Gnomad4 EAS AF: 0.0135

Gnomad4 SAS AF: 0.0443

Gnomad4 FIN AF: 0.0825

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0762

Alfa AF: 0.0433 Hom.: 46

Bravo AF: 0.0714

Asia WGS AF: 0.0330 AC: 117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.5
DANN	Benign	0.70

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: rs11603691; hg19: chr11-57107617;