12-121184760-G-T

Variant names:

• chr12-121184760-G-T
• rs1621388
• NM_002562.6:c.1746G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002562.6(P2RX7):​c.1746G>T​(p.Pro582Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: P2RX7 NM_002562.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265
• Publications: 23 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=0.265 with no splicing effect.

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.1746G>T	p.Pro582Pro	synonymous	Exon 13 of 13	NP_002553.3
	P2RX7	NR_033948.2		n.2064G>T		non_coding_transcript_exon	Exon 13 of 13
	P2RX7	NR_033949.2		n.1980G>T		non_coding_transcript_exon	Exon 14 of 14

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.1746G>T	p.Pro582Pro	synonymous	Exon 13 of 13	ENSP00000330696.6
	P2RX7	ENST00000261826.10	TSL:1	n.*1199G>T		non_coding_transcript_exon	Exon 12 of 12	ENSP00000261826.6
	P2RX7	ENST00000538011.5	TSL:1	n.*1501G>T		non_coding_transcript_exon	Exon 14 of 14	ENSP00000439247.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1400616 Hom.: 0 Cov.: 41 AF XY: 0.00 AC XY: 0 AN XY: 691050

African (AFR) AF: 0.00 AC: 0 AN: 31664

American (AMR) AF: 0.00 AC: 0 AN: 35912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25300

East Asian (EAS) AF: 0.00 AC: 0 AN: 35854

South Asian (SAS) AF: 0.00 AC: 0 AN: 79518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079826

Other (OTH) AF: 0.00 AC: 0 AN: 58092

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 8253

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.5
DANN	Benign	0.62
PhyloP100		0.27

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: rs1621388; hg19: chr12-121622563;