Variant chr17-3898140-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0940

Variant links:

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]

P2RX1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 link	c.1033-30C>T		intron_variant	Intron 10 of 11	ENST00000225538.4	NP_002549.1	P51575

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX1	ENST00000225538.4 link	c.1033-30C>T		intron_variant	Intron 10 of 11	1	NM_002558.4	ENSP00000225538.3		P51575
P2RX1	ENST00000572418.1 link	n.1556-30C>T		intron_variant	Intron 9 of 10	2

Frequencies

GnomAD3 genomes

AF:

0.0332

AC:

5037

AN:

151528

Hom.:

115

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0385

AC:

9625

AN:

250244

Hom.:

272

AF XY:

0.0418

AC XY:

5666

AN XY:

135428

show subpopulations

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 SAS exome

AF:

0.0705

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.:

AF XY:

0.0472

AC XY:

33730

AN XY:

715358

show subpopulations

Gnomad4 AFR exome

AF:

0.00619

Gnomad4 AMR exome

AF:

0.0198

Gnomad4 ASJ exome

AF:

0.0470

Gnomad4 EAS exome

AF:

0.000278

Gnomad4 SAS exome

AF:

0.0703

Gnomad4 FIN exome

AF:

0.0255

Gnomad4 NFE exome

AF:

0.0487

Gnomad4 OTH exome

AF:

0.0426

GnomAD4 genome

AF:

0.0332

AC:

5031

AN:

151646

Hom.:

114

Cov.:

AF XY:

0.0327

AC XY:

2420

AN XY:

74074

show subpopulations

Gnomad4 AFR

AF:

0.00897

Gnomad4 AMR

AF:

0.0282

Gnomad4 ASJ

AF:

0.0433

Gnomad4 EAS

AF:

0.00118

Gnomad4 SAS

AF:

0.0679

Gnomad4 FIN

AF:

0.0258

Gnomad4 NFE

AF:

0.0491

Gnomad4 OTH

AF:

0.0371

Alfa

AF:

0.0221

Hom.:

Bravo

AF:

0.0317

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over