rs3754376

Positions:

• chr1-226373363-C-A
• chr1-226373363-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.2070+863G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,074 control chromosomes in the GnomAD database, including 25,006 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 0.56 (25006 hom., cov: 32)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP1	NM_001618.4	c.2070+863G>T		intron_variant		ENST00000366794.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP1	ENST00000366794.10	c.2070+863G>T		intron_variant		1	NM_001618.4	P1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84458 AN: 151956 Hom.: 25011 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.592

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.556 AC: 84482 AN: 152074 Hom.: 25006 Cov.: 32 AF XY: 0.552 AC XY: 41048 AN XY: 74332

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.593

Alfa AF: 0.641 Hom.: 27493

Bravo AF: 0.538

Asia WGS AF: 0.454 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.76

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: rs3754376; hg19: chr1-226561064; COSMIC: COSV64689714; COSMIC: COSV64689714;