chr17-3898140-G-A

Variant names:

• chr17-3898140-G-A
• rs149912938
• NM_002558.4:c.1033-30C>T

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.1033-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 1,586,044 control chromosomes in the GnomAD database, including 1,888 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.033 (114 hom., cov: 30)
  • Exomes 𝑓: 0.046 (1774 hom.)
• Consequence: P2RX1 NM_002558.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0940

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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-3898140-G-A is Benign according to our data. Variant chr17-3898140-G-A is described in ClinVar as [Benign]. Clinvar id is 1228110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX1	NM_002558.4	c.1033-30C>T		intron_variant	Intron 10 of 11	ENST00000225538.4	NP_002549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX1	ENST00000225538.4	c.1033-30C>T		intron_variant	Intron 10 of 11	1	NM_002558.4	ENSP00000225538.3
P2RX1	ENST00000572418.1	n.1556-30C>T		intron_variant	Intron 9 of 10	2

Frequencies

GnomAD3 genomes AF: 0.0332 AC: 5037 AN: 151528 Hom.: 115 Cov.: 30

Gnomad AFR AF: 0.00903

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0283

Gnomad ASJ AF: 0.0433

Gnomad EAS AF: 0.00118

Gnomad SAS AF: 0.0679

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0491

Gnomad OTH AF: 0.0375

GnomAD2 exomes AF: 0.0385 AC: 9625 AN: 250244 AF XY: 0.0418

Gnomad AFR exome AF: 0.00710

Gnomad AMR exome AF: 0.0192

Gnomad ASJ exome AF: 0.0490

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0271

Gnomad NFE exome AF: 0.0473

Gnomad OTH exome AF: 0.0435

GnomAD4 exome AF: 0.0457 AC: 65520 AN: 1434398 Hom.: 1774 Cov.: 26 AF XY: 0.0472 AC XY: 33730 AN XY: 715358

Gnomad4 AFR exome AF: 0.00619 AC: 204 AN: 32946

Gnomad4 AMR exome AF: 0.0198 AC: 884 AN: 44684

Gnomad4 ASJ exome AF: 0.0470 AC: 1222 AN: 25976

Gnomad4 EAS exome AF: 0.000278 AC: 11 AN: 39552

Gnomad4 SAS exome AF: 0.0703 AC: 6026 AN: 85698

Gnomad4 FIN exome AF: 0.0255 AC: 1352 AN: 53028

Gnomad4 NFE exome AF: 0.0487 AC: 52901 AN: 1087358

Gnomad4 Remaining exome AF: 0.0426 AC: 2531 AN: 59478

GnomAD4 genome AF: 0.0332 AC: 5031 AN: 151646 Hom.: 114 Cov.: 30 AF XY: 0.0327 AC XY: 2420 AN XY: 74074

Gnomad4 AFR AF: 0.00897 AC: 0.00897436 AN: 0.00897436

Gnomad4 AMR AF: 0.0282 AC: 0.0282375 AN: 0.0282375

Gnomad4 ASJ AF: 0.0433 AC: 0.0432526 AN: 0.0432526

Gnomad4 EAS AF: 0.00118 AC: 0.00118064 AN: 0.00118064

Gnomad4 SAS AF: 0.0679 AC: 0.0679348 AN: 0.0679348

Gnomad4 FIN AF: 0.0258 AC: 0.0258016 AN: 0.0258016

Gnomad4 NFE AF: 0.0491 AC: 0.0490779 AN: 0.0490779

Gnomad4 OTH AF: 0.0371 AC: 0.0370722 AN: 0.0370722

Alfa AF: 0.0221 Hom.: 17

Bravo AF: 0.0317

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 21, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.54
DANN	Benign	0.61
BranchPoint Hunter		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs149912938; hg19: chr17-3801434;