chr12-121184717-T-A

Position:

• chr12-121184717-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The ENST00000328963.10(P2RX7):​c.1703T>A​(p.Ile568Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 1,562,934 control chromosomes in the GnomAD database, including 424 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.015 (24 hom., cov: 33)
  • Exomes 𝑓: 0.022 (400 hom.)
• Consequence: P2RX7 ENST00000328963.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11476803).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.015 (2289/152316) while in subpopulation NFE AF= 0.0245 (1667/68016). AF 95% confidence interval is 0.0235. There are 24 homozygotes in gnomad4. There are 1070 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.1703T>A	p.Ile568Asn	missense_variant	13/13	ENST00000328963.10	NP_002553.3
LOC105370032	XR_001749352.3	n.327+18781A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.1703T>A	p.Ile568Asn	missense_variant	13/13	1	NM_002562.6	ENSP00000330696	P1
	ENST00000652651.1	n.3548+1484A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2289 AN: 152198 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.00386

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.00799

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.0220 AC: 31022 AN: 1410618 Hom.: 400 Cov.: 37 AF XY: 0.0212 AC XY: 14797 AN XY: 697236

Gnomad4 AFR exome AF: 0.00260

Gnomad4 AMR exome AF: 0.00496

Gnomad4 ASJ exome AF: 0.00457

Gnomad4 EAS exome AF: 0.0000548

Gnomad4 SAS exome AF: 0.00329

Gnomad4 FIN exome AF: 0.0291

Gnomad4 NFE exome AF: 0.0258

Gnomad4 OTH exome AF: 0.0160

GnomAD4 genome AF: 0.0150 AC: 2289 AN: 152316 Hom.: 24 Cov.: 33 AF XY: 0.0144 AC XY: 1070 AN XY: 74490

Gnomad4 AFR AF: 0.00385

Gnomad4 AMR AF: 0.00798

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.0265

Gnomad4 NFE AF: 0.0245

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.0183 Hom.: 8

Bravo AF: 0.0130

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DEOGEN2	Uncertain	0.48	T
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.11	T
Sift4G	Pathogenic	0.0010	D
Vest4		0.72
gMVP		0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1653624; hg19: chr12-121622520;