rs2293464

Positions:

• chr1-226388595-G-A

Variant summary

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

The NM_001618.4(PARP1):​c.717+61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,184,648 control chromosomes in the GnomAD database, including 22,900 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 0.23 (4644 hom., cov: 33)
  • Exomes 𝑓: 0.18 (18256 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

Genes affected

PARP1 (HGNC:270): (poly(ADP-ribose) polymerase 1) This gene encodes a chromatin-associated enzyme, poly(ADP-ribosyl)transferase, which modifies various nuclear proteins by poly(ADP-ribosyl)ation. The modification is dependent on DNA and is involved in the regulation of various important cellular processes such as differentiation, proliferation, and tumor transformation and also in the regulation of the molecular events involved in the recovery of cell from DNA damage. In addition, this enzyme may be the site of mutation in Fanconi anemia, and may participate in the pathophysiology of type I diabetes. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP1	NM_001618.4	c.717+61C>T		intron_variant		ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.717+61C>T		intron_variant		1	NM_001618.4	ENSP00000355759	P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34263 AN: 152090 Hom.: 4641 Cov.: 33

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.182 AC: 187714 AN: 1032440 Hom.: 18256 AF XY: 0.181 AC XY: 96589 AN XY: 533452

Gnomad4 AFR exome AF: 0.385

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.327

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.225 AC: 34288 AN: 152208 Hom.: 4644 Cov.: 33 AF XY: 0.224 AC XY: 16637 AN XY: 74422

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.200

Alfa AF: 0.176 Hom.: 5131

Bravo AF: 0.233

Asia WGS AF: 0.244 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs2293464; hg19: chr1-226576296;