dbSNP rs1621388: P2RX7:p.Pro582Pro (chr12-121184760-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002562.6(P2RX7):c.1746G>A(p.Pro582Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,552,404 control chromosomes in the GnomAD database, including 118,313 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 0.39 ( 11789 hom., cov: 32)

Exomes 𝑓: 0.39 ( 106524 hom. )

Consequence

P2RX7
NM_002562.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.265

Variant links:

Genes affected

P2RX7 (HGNC:8537): (purinergic receptor P2X 7) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel and is responsible for ATP-dependent lysis of macrophages through the formation of membrane pores permeable to large molecules. Activation of this nuclear receptor by ATP in the cytoplasm may be a mechanism by which cellular activity can be coupled to changes in gene expression. Multiple alternatively spliced variants have been identified, most of which fit nonsense-mediated decay (NMD) criteria. [provided by RefSeq, Jul 2010]

P2RX7 links:

ENSG00000286248 (HGNC:):

ENSG00000286248 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP7

Synonymous conserved (PhyloP=0.265 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6 link	c.1746G>A	p.Pro582Pro	synonymous_variant	Exon 13 of 13	ENST00000328963.10	NP_002553.3	Q99572-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10 link	c.1746G>A	p.Pro582Pro	synonymous_variant	Exon 13 of 13	1	NM_002562.6	ENSP00000330696.6		Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.386

AC:

58657

AN:

151942

Hom.:

11767

Cov.:

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.396

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.271

Gnomad NFE

AF:

0.399

Gnomad OTH

AF:

0.362

GnomAD3 exomes

AF:

0.344

AC:

54214

AN:

157728

Hom.:

10360

AF XY:

0.351

AC XY:

29480

AN XY:

83914

show subpopulations

Gnomad AFR exome

AF:

0.459

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.351

Gnomad EAS exome

AF:

0.112

Gnomad SAS exome

AF:

0.385

Gnomad FIN exome

AF:

0.455

Gnomad NFE exome

AF:

0.395

Gnomad OTH exome

AF:

0.348

GnomAD4 exome

AF:

0.386

AC:

540202

AN:

1400344

Hom.:

106524

Cov.:

AF XY:

0.386

AC XY:

266419

AN XY:

690920

show subpopulations

Gnomad4 AFR exome

AF:

0.463

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.354

Gnomad4 EAS exome

AF:

0.143

Gnomad4 SAS exome

AF:

0.385

Gnomad4 FIN exome

AF:

0.446

Gnomad4 NFE exome

AF:

0.397

Gnomad4 OTH exome

AF:

0.373

GnomAD4 genome

AF:

0.386

AC:

58725

AN:

152060

Hom.:

11789

Cov.:

AF XY:

0.381

AC XY:

28305

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.443

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.344

Gnomad4 EAS

AF:

0.127

Gnomad4 SAS

AF:

0.358

Gnomad4 FIN

AF:

0.449

Gnomad4 NFE

AF:

0.399

Gnomad4 OTH

AF:

0.357

Alfa

AF:

0.371

Hom.:

7261

Bravo

AF:

0.369

Asia WGS

AF:

0.264

AC:

917

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.86

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over