rs1007637

chr17-3914315-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002558.4(P2RX1):c.137+1774C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 151,736 control chromosomes in the GnomAD database, including 3,462 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 0.20 (3462 hom., cov: 30)
• Consequence: P2RX1 NM_002558.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

Genes affected

P2RX1 (HGNC:8533): (purinergic receptor P2X 1) The protein encoded by this gene belongs to the P2X family of G-protein-coupled receptors. These proteins can form homo-and heterotimers and function as ATP-gated ion channels and mediate rapid and selective permeability to cations. This protein is primarily localized to smooth muscle where binds ATP and mediates synaptic transmission between neurons and from neurons to smooth muscle and may being responsible for sympathetic vasoconstriction in small arteries, arterioles and vas deferens. Mouse studies suggest that this receptor is essential for normal male reproductive function. This protein may also be involved in promoting apoptosis. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX1	NM_002558.4	c.137+1774C>T		intron_variant		ENST00000225538.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX1	ENST00000225538.4	c.137+1774C>T		intron_variant		1	NM_002558.4	P1
P2RX1	ENST00000571637.1	c.*596+1031C>T		intron_variant, NMD_transcript_variant		1
P2RX1	ENST00000572418.1	n.364+1774C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30432 AN: 151618 Hom.: 3463 Cov.: 30

Gnomad AFR AF: 0.0924

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.201 AC: 30440 AN: 151736 Hom.: 3462 Cov.: 30 AF XY: 0.203 AC XY: 15048 AN XY: 74116

Gnomad4 AFR AF: 0.0925

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.224

Alfa AF: 0.243 Hom.: 7592

Bravo AF: 0.197

Asia WGS AF: 0.290 AC: 1011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.7
Dann	Benign	0.53

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: rs1007637; hg19: chr17-3817609; COSMIC: COSV56655601;