17-3682483-C-G

Position:

• chr17-3682483-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000225328.10(P2RX5):​c.982-505G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 203,722 control chromosomes in the GnomAD database, including 22,315 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 0.44 (16050 hom., cov: 33)
  • Exomes 𝑓: 0.49 (6265 hom.)
• Consequence: P2RX5 ENST00000225328.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129

Genes affected

P2RX5 (HGNC:8536): (purinergic receptor P2X 5) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream gene, TAX1BP3 (Tax1 binding protein 3). [provided by RefSeq, Mar 2011]

P2RX5-TAX1BP3 (HGNC:49191): (P2RX5-TAX1BP3 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring P2RX5 (purinergic receptor P2X, ligand-gated ion channel, 5) and TAX1BP3 (Tax1 binding protein 3) genes on chromosome 17. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

P2RX5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX5	NM_002561.4	c.982-505G>C		intron_variant		ENST00000225328.10	NP_002552.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX5	ENST00000225328.10	c.982-505G>C		intron_variant		1	NM_002561.4	ENSP00000225328.5
P2RX5	ENST00000697413.1	c.1048-505G>C		intron_variant				ENSP00000513301.1
P2RX5-TAX1BP3	ENST00000550383.1	n.982-505G>C		intron_variant		2		ENSP00000455681.1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67135 AN: 152022 Hom.: 16052 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.469

GnomAD4 exome AF: 0.487 AC: 25096 AN: 51582 Hom.: 6265 Cov.: 0 AF XY: 0.488 AC XY: 13432 AN XY: 27528

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.474

Gnomad4 ASJ exome AF: 0.491

Gnomad4 EAS exome AF: 0.459

Gnomad4 SAS exome AF: 0.516

Gnomad4 FIN exome AF: 0.493

Gnomad4 NFE exome AF: 0.501

Gnomad4 OTH exome AF: 0.465

GnomAD4 genome AF: 0.441 AC: 67163 AN: 152140 Hom.: 16050 Cov.: 33 AF XY: 0.444 AC XY: 33021 AN XY: 74378

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.468

Alfa AF: 0.468 Hom.: 2166

Bravo AF: 0.429

Asia WGS AF: 0.498 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs222775; hg19: chr17-3585777; COSMIC: COSV56593653; COSMIC: COSV56593653;