Genetic Variant NM_002562.6:c.437-47C>T (chr12-121162377-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002562.6(P2RX7):c.437-47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,607,898 control chromosomes in the GnomAD database, including 88,479 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 0.42 ( 16320 hom., cov: 31)

Exomes 𝑓: 0.30 ( 72159 hom. )

Consequence

P2RX7
NM_002562.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.797

Publications

13 publications found

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:

ENSG00000295862 (HGNC:):

ENSG00000295862 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6 link	c.437-47C>T		intron_variant	Intron 4 of 12	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.437-47C>T		intron_variant	Intron 4 of 12	1	NM_002562.6	ENSP00000330696.6		Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

63124

AN:

151876

Hom.:

16258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.733

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.414

Gnomad FIN

AF:

0.395

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.340

GnomAD2 exomes

AF:

0.324

AC:

78843

AN:

243444

AF XY:

0.322

show subpopulations

Gnomad AFR exome

AF:

0.748

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.209

Gnomad EAS exome

AF:

0.390

Gnomad FIN exome

AF:

0.406

Gnomad NFE exome

AF:

0.276

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.302

AC:

439160

AN:

1455904

Hom.:

72159

Cov.:

AF XY:

0.303

AC XY:

219600

AN XY:

723846

show subpopulations

African (AFR)

AF:

0.753

AC:

25132

AN:

33392

American (AMR)

AF:

0.172

AC:

7572

AN:

44142

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

5452

AN:

25896

East Asian (EAS)

AF:

0.413

AC:

16339

AN:

39558

South Asian (SAS)

AF:

0.404

AC:

34586

AN:

85540

European-Finnish (FIN)

AF:

0.401

AC:

20843

AN:

52020

Middle Eastern (MID)

AF:

0.228

AC:

1312

AN:

5750

European-Non Finnish (NFE)

AF:

0.278

AC:

308840

AN:

1109444

Other (OTH)

AF:

0.317

AC:

19084

AN:

60162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

13517

27033

40550

54066

67583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10562

21124

31686

42248

52810

<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:

0.416

AC:

63262

AN:

151994

Hom.:

16320

Cov.:

AF XY:

0.415

AC XY:

30826

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.734

AC:

30404

AN:

41430

American (AMR)

AF:

0.247

AC:

3765

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

739

AN:

3472

East Asian (EAS)

AF:

0.399

AC:

2057

AN:

5156

South Asian (SAS)

AF:

0.416

AC:

2006

AN:

4820

European-Finnish (FIN)

AF:

0.395

AC:

4168

AN:

10558

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.282

AC:

19152

AN:

67974

Other (OTH)

AF:

0.342

AC:

722

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1618

3237

4855

6474

8092

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.325

Hom.:

7129

Bravo

AF:

0.414

Asia WGS

AF:

0.429

AC:

1493

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.1

(source)

DANN

Benign

0.75

PhyloP100

-0.80

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over