chr17-3897786-C-T

Variant names:

• chr17-3897786-C-T
• rs711174
• NM_002558.4:c.*28G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002558.4(P2RX1):​c.*28G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,605,494 control chromosomes in the GnomAD database, including 94,566 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6801 hom., cov: 31)
  • Exomes 𝑓: 0.34 (87765 hom.)
• Consequence: P2RX1 NM_002558.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.80
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-3897786-C-T is Benign according to our data. Variant chr17-3897786-C-T is described in ClinVar as Benign. ClinVar VariationId is 1268219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002558.4. 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
	P2RX1	NM_002558.4	MANE Select	c.*28G>A		3_prime_UTR	Exon 12 of 12	NP_002549.1	P51575

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX1	ENST00000225538.4	TSL:1 MANE Select	c.*28G>A		3_prime_UTR	Exon 12 of 12	ENSP00000225538.3	P51575
	P2RX1	ENST00000968389.1		c.*28G>A		3_prime_UTR	Exon 12 of 12	ENSP00000638448.1
	P2RX1	ENST00000861554.1		c.*28G>A		3_prime_UTR	Exon 12 of 12	ENSP00000531613.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43259 AN: 151954 Hom.: 6802 Cov.: 31

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.0721

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.274

GnomAD2 exomes AF: 0.268 AC: 66063 AN: 246436 AF XY: 0.270

Gnomad AFR exome AF: 0.211

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.301

Gnomad EAS exome AF: 0.0709

Gnomad FIN exome AF: 0.323

Gnomad NFE exome AF: 0.363

Gnomad OTH exome AF: 0.284

GnomAD4 exome AF: 0.337 AC: 489534 AN: 1453422 Hom.: 87765 Cov.: 30 AF XY: 0.332 AC XY: 239833 AN XY: 723342

African (AFR) AF: 0.212 AC: 7073 AN: 33292

American (AMR) AF: 0.151 AC: 6725 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 7928 AN: 26086

East Asian (EAS) AF: 0.0620 AC: 2456 AN: 39610

South Asian (SAS) AF: 0.162 AC: 13927 AN: 85920

European-Finnish (FIN) AF: 0.328 AC: 17308 AN: 52810

Middle Eastern (MID) AF: 0.229 AC: 978 AN: 4270

European-Non Finnish (NFE) AF: 0.374 AC: 414101 AN: 1106924

Other (OTH) AF: 0.318 AC: 19038 AN: 59960

GnomAD4 genome AF: 0.284 AC: 43262 AN: 152072 Hom.: 6801 Cov.: 31 AF XY: 0.276 AC XY: 20546 AN XY: 74328

African (AFR) AF: 0.213 AC: 8820 AN: 41504

American (AMR) AF: 0.218 AC: 3334 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1024 AN: 3466

East Asian (EAS) AF: 0.0719 AC: 370 AN: 5144

South Asian (SAS) AF: 0.141 AC: 683 AN: 4830

European-Finnish (FIN) AF: 0.326 AC: 3446 AN: 10580

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24569 AN: 67944

Other (OTH) AF: 0.270 AC: 571 AN: 2112

Alfa AF: 0.326 Hom.: 11062

Bravo AF: 0.276

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.61
DANN	Benign	0.60
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs711174; hg19: chr17-3801080; COSMIC: COSV50114621; COSMIC: COSV50114621;