Genetic Variant NM_002562.6: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6 link	c.1189-16A>C		intron_variant	Intron 11 of 12	ENST00000328963.10	NP_002553.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10 link	c.1189-16A>C		intron_variant	Intron 11 of 12	1	NM_002562.6	ENSP00000330696.6

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over