rs2230913

Variant names:

• chr12-121184577-C-G
• rs2230913
• NM_002562.6:c.1563C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-121184577-C-G
• chr12-121184577-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002562.6(P2RX7):​c.1563C>G​(p.His521Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0071 in 1,614,104 control chromosomes in the GnomAD database, including 728 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.038 (366 hom., cov: 33)
  • Exomes 𝑓: 0.0039 (362 hom.)
• Consequence: P2RX7 NM_002562.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.05
• Publications: 17 publications found

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]

ENSG00000286248 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014154017).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	NM_002562.6	MANE Select	c.1563C>G	p.His521Gln	missense	Exon 13 of 13	NP_002553.3
	P2RX7	NR_033948.2		n.1881C>G		non_coding_transcript_exon	Exon 13 of 13
	P2RX7	NR_033949.2		n.1797C>G		non_coding_transcript_exon	Exon 14 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.1563C>G	p.His521Gln	missense	Exon 13 of 13	ENSP00000330696.6	Q99572-1
	P2RX7	ENST00000261826.10	TSL:1	n.*1016C>G		non_coding_transcript_exon	Exon 12 of 12	ENSP00000261826.6	J3KN30
	P2RX7	ENST00000538011.5	TSL:1	n.*1318C>G		non_coding_transcript_exon	Exon 14 of 14	ENSP00000439247.1	F5H2X6

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5709 AN: 152212 Hom.: 360 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0133

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0258

GnomAD2 exomes AF: 0.0102 AC: 2554 AN: 250558 AF XY: 0.00751

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.00651

Gnomad ASJ exome AF: 0.000897

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000459

Gnomad OTH exome AF: 0.00474

GnomAD4 exome AF: 0.00391 AC: 5719 AN: 1461774 Hom.: 362 Cov.: 40 AF XY: 0.00344 AC XY: 2499 AN XY: 727186

African (AFR) AF: 0.135 AC: 4513 AN: 33472

American (AMR) AF: 0.00783 AC: 350 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.000804 AC: 21 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00676 AC: 39 AN: 5768

European-Non Finnish (NFE) AF: 0.000239 AC: 266 AN: 1111990

Other (OTH) AF: 0.00841 AC: 508 AN: 60394

GnomAD4 genome AF: 0.0377 AC: 5741 AN: 152330 Hom.: 366 Cov.: 33 AF XY: 0.0361 AC XY: 2693 AN XY: 74498

African (AFR) AF: 0.131 AC: 5446 AN: 41566

American (AMR) AF: 0.0133 AC: 204 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68036

Other (OTH) AF: 0.0255 AC: 54 AN: 2114

Alfa AF: 0.00217 Hom.: 7

Bravo AF: 0.0434

ESP6500AA AF: 0.140 AC: 615

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.0128 AC: 1552

Asia WGS AF: 0.00953 AC: 33 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000534

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.0010
DANN	Benign	0.55
DEOGEN2	Benign	0.068	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		-6.1
PrimateAI	Benign	0.29	T
REVEL	Benign	0.054
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.030
MutPred		0.12		Loss of catalytic residue at L523 (P = 0.1094)
ClinPred		0.0060	T
GERP RS		-10
Varity_R		0.029
gMVP		0.19
Mutation Taster		=86/14	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2230913; hg19: chr12-121622380;