chr12-121145948-C-G

Variant names:

• chr12-121145948-C-G
• rs169631
• NM_002562.6:c.126-8837C>G

Variant summary

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

The NM_002562.6(P2RX7):​c.126-8837C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 151,916 control chromosomes in the GnomAD database, including 16,965 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 (16965 hom., cov: 31)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301
• Publications: 2 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]

LOC105370032 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 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.126-8837C>G		intron	N/A	NP_002553.3
	P2RX7	NR_033948.2		n.221-8837C>G		intron	N/A
	P2RX7	NR_033949.2		n.221-8837C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.126-8837C>G		intron	N/A	ENSP00000330696.6	Q99572-1
	P2RX7	ENST00000261826.10	TSL:1	n.126-8837C>G		intron	N/A	ENSP00000261826.6	J3KN30
	P2RX7	ENST00000538011.5	TSL:1	n.126-8837C>G		intron	N/A	ENSP00000439247.1	F5H2X6

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63813 AN: 151798 Hom.: 16907 Cov.: 31

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.345

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.421 AC: 63941 AN: 151916 Hom.: 16965 Cov.: 31 AF XY: 0.419 AC XY: 31069 AN XY: 74228

African (AFR) AF: 0.758 AC: 31425 AN: 41434

American (AMR) AF: 0.244 AC: 3725 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 743 AN: 3468

East Asian (EAS) AF: 0.379 AC: 1954 AN: 5158

South Asian (SAS) AF: 0.423 AC: 2030 AN: 4798

European-Finnish (FIN) AF: 0.376 AC: 3960 AN: 10528

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19121 AN: 67952

Other (OTH) AF: 0.346 AC: 731 AN: 2112

Alfa AF: 0.198 Hom.: 427

Bravo AF: 0.420

Asia WGS AF: 0.430 AC: 1497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.36
PhyloP100		-0.30
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: rs169631; hg19: chr12-121583751;