rs2280712

chr1-226392392-C-T

Variant summary

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

The NM_001618.4(PARP1):c.287-78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 954,124 control chromosomes in the GnomAD database, including 13,768 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 0.13 (1763 hom., cov: 32)
  • Exomes 𝑓: 0.16 (12005 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP1	NM_001618.4	c.287-78G>A		intron_variant		ENST00000366794.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP1	ENST00000366794.10	c.287-78G>A		intron_variant		1	NM_001618.4	P1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20553 AN: 152098 Hom.: 1766 Cov.: 32

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.163 AC: 131056 AN: 801908 Hom.: 12005 AF XY: 0.166 AC XY: 70598 AN XY: 425508

Gnomad4 AFR exome AF: 0.0499

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.325

Gnomad4 SAS exome AF: 0.180

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.135 AC: 20536 AN: 152216 Hom.: 1763 Cov.: 32 AF XY: 0.137 AC XY: 10160 AN XY: 74426

Gnomad4 AFR AF: 0.0518

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.136

Alfa AF: 0.152 Hom.: 703

Bravo AF: 0.129

Asia WGS AF: 0.230 AC: 801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	0.84
Dann	Benign	0.87

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: rs2280712; hg19: chr1-226580093; COSMIC: COSV64687766; COSMIC: COSV64687766;