chr12-121162377-C-T

Variant names:

• chr12-121162377-C-T
• rs208293
• NM_002562.6:c.437-47C>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.437-47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,607,898 control chromosomes in the GnomAD database, including 88,479 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 0.42 (16320 hom., cov: 31)
  • Exomes 𝑓: 0.30 (72159 hom.)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797
• Publications: 13 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]

ENSG00000295862 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	NM_002562.6	MANE Select	c.437-47C>T		intron	N/A	NP_002553.3
	P2RX7	NR_033950.2		n.638C>T		non_coding_transcript_exon	Exon 5 of 11
	P2RX7	NR_033948.2		n.671-47C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.437-47C>T		intron	N/A	ENSP00000330696.6
	P2RX7	ENST00000261826.10	TSL:1	n.436+1403C>T		intron	N/A	ENSP00000261826.6
	P2RX7	ENST00000538011.5	TSL:1	n.*192-47C>T		intron	N/A	ENSP00000439247.1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63124 AN: 151876 Hom.: 16258 Cov.: 31

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.340

GnomAD2 exomes AF: 0.324 AC: 78843 AN: 243444 AF XY: 0.322

Gnomad AFR exome AF: 0.748

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.390

Gnomad FIN exome AF: 0.406

Gnomad NFE exome AF: 0.276

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.302 AC: 439160 AN: 1455904 Hom.: 72159 Cov.: 32 AF XY: 0.303 AC XY: 219600 AN XY: 723846

African (AFR) AF: 0.753 AC: 25132 AN: 33392

American (AMR) AF: 0.172 AC: 7572 AN: 44142

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 5452 AN: 25896

East Asian (EAS) AF: 0.413 AC: 16339 AN: 39558

South Asian (SAS) AF: 0.404 AC: 34586 AN: 85540

European-Finnish (FIN) AF: 0.401 AC: 20843 AN: 52020

Middle Eastern (MID) AF: 0.228 AC: 1312 AN: 5750

European-Non Finnish (NFE) AF: 0.278 AC: 308840 AN: 1109444

Other (OTH) AF: 0.317 AC: 19084 AN: 60162

GnomAD4 genome AF: 0.416 AC: 63262 AN: 151994 Hom.: 16320 Cov.: 31 AF XY: 0.415 AC XY: 30826 AN XY: 74288

African (AFR) AF: 0.734 AC: 30404 AN: 41430

American (AMR) AF: 0.247 AC: 3765 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3472

East Asian (EAS) AF: 0.399 AC: 2057 AN: 5156

South Asian (SAS) AF: 0.416 AC: 2006 AN: 4820

European-Finnish (FIN) AF: 0.395 AC: 4168 AN: 10558

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19152 AN: 67974

Other (OTH) AF: 0.342 AC: 722 AN: 2114

Alfa AF: 0.325 Hom.: 7129

Bravo AF: 0.414

Asia WGS AF: 0.429 AC: 1493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.75
PhyloP100		-0.80
Mutation Taster		=100/0	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: rs208293; hg19: chr12-121600180;