rs3751143

Variant names:

• chr12-121184501-A-C
• rs3751143
• NM_002562.6:c.1487A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-121184501-A-C
• chr12-121184501-A-G
• chr12-121184501-A-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.1487A>C​(p.Glu496Ala) variant causes a missense change. The variant allele was found at a frequency of 0.182 in 1,613,952 control chromosomes in the GnomAD database, including 28,127 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 0.16 (2070 hom., cov: 32)
  • Exomes 𝑓: 0.18 (26057 hom.)
• Consequence: P2RX7 NM_002562.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.51
• Publications: 246 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=0.0016499162).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 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.1487A>C	p.Glu496Ala	missense	Exon 13 of 13	NP_002553.3
	P2RX7	NR_033948.2		n.1805A>C		non_coding_transcript_exon	Exon 13 of 13
	P2RX7	NR_033949.2		n.1721A>C		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.1487A>C	p.Glu496Ala	missense	Exon 13 of 13	ENSP00000330696.6	Q99572-1
	P2RX7	ENST00000261826.10	TSL:1	n.*940A>C		non_coding_transcript_exon	Exon 12 of 12	ENSP00000261826.6	J3KN30
	P2RX7	ENST00000538011.5	TSL:1	n.*1242A>C		non_coding_transcript_exon	Exon 14 of 14	ENSP00000439247.1	F5H2X6

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24107 AN: 152076 Hom.: 2078 Cov.: 32

Gnomad AFR AF: 0.0934

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.202

GnomAD2 exomes AF: 0.189 AC: 47509 AN: 251024 AF XY: 0.197

Gnomad AFR exome AF: 0.0886

Gnomad AMR exome AF: 0.182

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.256

Gnomad FIN exome AF: 0.105

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.205

GnomAD4 exome AF: 0.185 AC: 270026 AN: 1461758 Hom.: 26057 Cov.: 61 AF XY: 0.189 AC XY: 137326 AN XY: 727178

African (AFR) AF: 0.0921 AC: 3082 AN: 33478

American (AMR) AF: 0.183 AC: 8200 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 5037 AN: 26134

East Asian (EAS) AF: 0.274 AC: 10891 AN: 39696

South Asian (SAS) AF: 0.281 AC: 24256 AN: 86248

European-Finnish (FIN) AF: 0.108 AC: 5785 AN: 53404

Middle Eastern (MID) AF: 0.262 AC: 1510 AN: 5768

European-Non Finnish (NFE) AF: 0.180 AC: 199850 AN: 1111944

Other (OTH) AF: 0.189 AC: 11415 AN: 60390

GnomAD4 genome AF: 0.158 AC: 24097 AN: 152194 Hom.: 2070 Cov.: 32 AF XY: 0.159 AC XY: 11860 AN XY: 74396

African (AFR) AF: 0.0932 AC: 3874 AN: 41546

American (AMR) AF: 0.178 AC: 2723 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 686 AN: 3468

East Asian (EAS) AF: 0.258 AC: 1335 AN: 5166

South Asian (SAS) AF: 0.289 AC: 1390 AN: 4818

European-Finnish (FIN) AF: 0.102 AC: 1080 AN: 10600

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12337 AN: 68002

Other (OTH) AF: 0.205 AC: 432 AN: 2108

Alfa AF: 0.184 Hom.: 12262

Bravo AF: 0.160

TwinsUK AF: 0.171 AC: 633

ALSPAC AF: 0.170 AC: 657

ESP6500AA AF: 0.0899 AC: 396

ESP6500EA AF: 0.185 AC: 1590

ExAC AF: 0.190 AC: 23012

Asia WGS AF: 0.274 AC: 951 AN: 3478

EpiCase AF: 0.194

EpiControl AF: 0.199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		6.5
PrimateAI	Benign	0.44	T
REVEL	Benign	0.20
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.13
ClinPred		0.011	T
GERP RS		5.2
Varity_R		0.23
gMVP		0.49
Mutation Taster		=96/4	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: rs3751143; hg19: chr12-121622304; COSMIC: COSV55853761;