1-226402008-C-T

Position:

• chr1-226402008-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.286+206G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,485,744 control chromosomes in the GnomAD database, including 105,456 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 (16357 hom., cov: 33)
  • Exomes 𝑓: 0.35 (89099 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.593

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]

PARP1 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP1	NM_001618.4	c.286+206G>A		intron_variant		ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.286+206G>A		intron_variant		1	NM_001618.4	ENSP00000355759.5

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67170 AN: 151890 Hom.: 16327 Cov.: 33

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.404

GnomAD3 exomes AF: 0.429 AC: 46898 AN: 109316 Hom.: 11445 AF XY: 0.418 AC XY: 23987 AN XY: 57360

Gnomad AFR exome AF: 0.628

Gnomad AMR exome AF: 0.520

Gnomad ASJ exome AF: 0.312

Gnomad EAS exome AF: 0.816

Gnomad SAS exome AF: 0.352

Gnomad FIN exome AF: 0.406

Gnomad NFE exome AF: 0.320

Gnomad OTH exome AF: 0.379

GnomAD4 exome AF: 0.352 AC: 469959 AN: 1333736 Hom.: 89099 Cov.: 33 AF XY: 0.352 AC XY: 228467 AN XY: 649880

Gnomad4 AFR exome AF: 0.628

Gnomad4 AMR exome AF: 0.505

Gnomad4 ASJ exome AF: 0.306

Gnomad4 EAS exome AF: 0.793

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.401

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.376

GnomAD4 genome AF: 0.443 AC: 67264 AN: 152008 Hom.: 16357 Cov.: 33 AF XY: 0.446 AC XY: 33150 AN XY: 74310

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.404

Alfa AF: 0.343 Hom.: 9868

Bravo AF: 0.459

Asia WGS AF: 0.548 AC: 1908 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	1.4
DANN	Benign	0.73

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: rs2666428; hg19: chr1-226589709; COSMIC: COSV104680319;