dbSNP rs2567998: P2RX7:c.1189-16A>C (chr12-121180338-A-C) – 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.1189-16A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,472,950 control chromosomes in the GnomAD database, including 172 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 0.019 ( 101 hom., cov: 31)

Exomes 𝑓: 0.0019 ( 71 hom. )

Consequence

P2RX7
NM_002562.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0760

Publications

3 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:

ENSG00000286248 (HGNC:):

ENSG00000286248 links:

Genome browser will be placed here

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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0633 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002562.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
P2RX7	NM_002562.6	MANE Select	c.1189-16A>C	intron	N/A	NP_002553.3
P2RX7	NR_033948.2		n.1507-16A>C	intron	N/A
P2RX7	NR_033949.2		n.1423-16A>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.1189-16A>C	intron	N/A	ENSP00000330696.6	Q99572-1
P2RX7	ENST00000261826.10	TSL:1	n.*642-16A>C	intron	N/A	ENSP00000261826.6	J3KN30
P2RX7	ENST00000538011.5	TSL:1	n.*944-16A>C	intron	N/A	ENSP00000439247.1	F5H2X6

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2876

AN:

152100

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00872

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00541

AC:

1183

AN:

218478

AF XY:

0.00408

show subpopulations

Gnomad AFR exome

AF:

0.0682

Gnomad AMR exome

AF:

0.00400

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00331

GnomAD4 exome

AF:

0.00190

AC:

2511

AN:

1320734

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1080

AN XY:

662590

show subpopulations

African (AFR)

AF:

0.0699

AC:

2042

AN:

29194

American (AMR)

AF:

0.00404

AC:

134

AN:

33134

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23758

East Asian (EAS)

AF:

0.00

AC:

AN:

38520

South Asian (SAS)

AF:

0.000196

AC:

AN:

76470

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52636

Middle Eastern (MID)

AF:

0.000932

AC:

AN:

5364

European-Non Finnish (NFE)

AF:

0.0000775

AC:

AN:

1006660

Other (OTH)

AF:

0.00431

AC:

237

AN:

54998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

100

201

301

402

502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.0190

AC:

2887

AN:

152216

Hom.:

101

Cov.:

AF XY:

0.0183

AC XY:

1363

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0654

AC:

2715

AN:

41516

American (AMR)

AF:

0.00871

AC:

133

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68020

Other (OTH)

AF:

0.0151

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

131

262

393

524

655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00481

Hom.:

Bravo

AF:

0.0217

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.85

(source)

DANN

Benign

0.55

PhyloP100

-0.076

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over