1-226388569-A-G

Position:

• chr1-226388569-A-G

Variant summary

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

The NM_001618.4(PARP1):​c.717+87T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 933,016 control chromosomes in the GnomAD database, including 21,663 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 0.19 (3240 hom., cov: 33)
  • Exomes 𝑓: 0.20 (18423 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP1	NM_001618.4	c.717+87T>C		intron_variant		ENST00000366794.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP1	ENST00000366794.10	c.717+87T>C		intron_variant		1	NM_001618.4	P1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28835 AN: 152128 Hom.: 3228 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.198 AC: 154880 AN: 780770 Hom.: 18423 AF XY: 0.194 AC XY: 80613 AN XY: 415112

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.407

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.466

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.193

GnomAD4 genome AF: 0.190 AC: 28899 AN: 152246 Hom.: 3240 Cov.: 33 AF XY: 0.196 AC XY: 14572 AN XY: 74430

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.187

Alfa AF: 0.170 Hom.: 353

Bravo AF: 0.196

Asia WGS AF: 0.298 AC: 1035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.4
DANN	Benign	0.43

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: rs2255403; hg19: chr1-226576270; COSMIC: COSV64687805; COSMIC: COSV64687805;