Genetic Variant P2RX7:c.364-53G>A (chr12-121160849-G-A) – 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.364-53G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 1,325,298 control chromosomes in the GnomAD database, including 5,203 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 0.10 ( 965 hom., cov: 32)

Exomes 𝑓: 0.080 ( 4238 hom. )

Consequence

P2RX7
NM_002562.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.776

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:

LOC105370032 (HGNC:):

LOC105370032 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6 link	c.364-53G>A		intron_variant	Intron 3 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.364-53G>A		intron_variant	Intron 3 of 12	1	NM_002562.6	ENSP00000330696.6		Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15509

AN:

152048

Hom.:

964

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0536

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.0664

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.0668

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0786

Gnomad OTH

AF:

0.0927

GnomAD4 exome

AF:

0.0799

AC:

93709

AN:

1173132

Hom.:

4238

AF XY:

0.0807

AC XY:

48277

AN XY:

597970

show subpopulations

African (AFR)

AF:

0.182

AC:

5060

AN:

27744

American (AMR)

AF:

0.0378

AC:

1677

AN:

44352

Ashkenazi Jewish (ASJ)

AF:

0.0425

AC:

1033

AN:

24302

East Asian (EAS)

AF:

0.0624

AC:

2401

AN:

38452

South Asian (SAS)

AF:

0.114

AC:

9198

AN:

80508

European-Finnish (FIN)

AF:

0.0694

AC:

3701

AN:

53304

Middle Eastern (MID)

AF:

0.0738

AC:

387

AN:

5246

European-Non Finnish (NFE)

AF:

0.0779

AC:

66065

AN:

848386

Other (OTH)

AF:

0.0824

AC:

4187

AN:

50838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

4462

8924

13386

17848

22310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.102

AC:

15523

AN:

152166

Hom.:

965

Cov.:

AF XY:

0.0992

AC XY:

7380

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.177

AC:

7338

AN:

41480

American (AMR)

AF:

0.0535

AC:

818

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0409

AC:

142

AN:

3468

East Asian (EAS)

AF:

0.0659

AC:

342

AN:

5186

South Asian (SAS)

AF:

0.113

AC:

544

AN:

4824

European-Finnish (FIN)

AF:

0.0668

AC:

707

AN:

10590

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0786

AC:

5345

AN:

68010

Other (OTH)

AF:

0.0918

AC:

194

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

695

1390

2085

2780

3475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0751

Hom.:

296

Bravo

AF:

0.103

Asia WGS

AF:

0.0890

AC:

309

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.27

(source)

DANN

Benign

0.83

PhyloP100

-0.78

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

LitVar

Below is the list of publications found by LitVar for variant 12:121160849 G>A . It may be empty.

chr12-121160849-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over