Genetic Variant P2RX1:p.Arg381His (chr17-3897872-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_002558.4(P2RX1):c.1142G>A(p.Arg381His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,613,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

P2RX1
NM_002558.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.89

Publications

2 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030875504).

BP6

Variant 17-3897872-C-T is Benign according to our data. Variant chr17-3897872-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3053327.Status of the report is no_assertion_criteria_provided, 0 stars.

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.1142G>A	p.Arg381His	missense	Exon 12 of 12	NP_002549.1	P51575

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
P2RX1	ENST00000225538.4	TSL:1 MANE Select	c.1142G>A	p.Arg381His	missense	Exon 12 of 12	ENSP00000225538.3	P51575
P2RX1	ENST00000968389.1		c.1202G>A	p.Arg401His	missense	Exon 12 of 12	ENSP00000638448.1
P2RX1	ENST00000861554.1		c.1091G>A	p.Arg364His	missense	Exon 12 of 12	ENSP00000531613.1

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

240

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00561

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000471

AC:

118

AN:

250644

AF XY:

0.000369

show subpopulations

Gnomad AFR exome

AF:

0.00591

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.0000531

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000167

AC:

244

AN:

1461716

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

113

AN XY:

727146

show subpopulations

African (AFR)

AF:

0.00502

AC:

168

AN:

33474

American (AMR)

AF:

0.000268

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5656

European-Non Finnish (NFE)

AF:

0.0000387

AC:

AN:

1112002

Other (OTH)

AF:

0.000248

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00156

AC:

238

AN:

152168

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

104

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.00554

AC:

230

AN:

41510

American (AMR)

AF:

0.000131

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000723

Hom.:

Bravo

AF:

0.00154

ESP6500AA

AF:

0.00545

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000585

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

P2RX1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.080

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.22

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0041

LIST_S2

Benign

0.72

M_CAP

Benign

0.0051

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

PhyloP100

-2.9

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.31

REVEL

Benign

0.014

Sift

Benign

0.48

Sift4G

Benign

0.21

Polyphen

0.0

Vest4

0.070

MVP

0.16

MPC

0.41

ClinPred

0.0026

GERP RS

-5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.021

gMVP

0.34

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over