1-226363828-C-G

Position:

• chr1-226363828-C-G

Variant summary

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

The NM_001618.4(PARP1):​c.2786+115G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 1,048,236 control chromosomes in the GnomAD database, including 356,254 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 0.82 (51774 hom., cov: 32)
  • Exomes 𝑓: 0.82 (304480 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP1	NM_001618.4	c.2786+115G>C		intron_variant		ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.2786+115G>C		intron_variant		1	NM_001618.4	ENSP00000355759	P1

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124852 AN: 152062 Hom.: 51758 Cov.: 32

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.823

GnomAD4 exome AF: 0.820 AC: 734809 AN: 896056 Hom.: 304480 AF XY: 0.826 AC XY: 385296 AN XY: 466740

Gnomad4 AFR exome AF: 0.872

Gnomad4 AMR exome AF: 0.593

Gnomad4 ASJ exome AF: 0.844

Gnomad4 EAS exome AF: 0.582

Gnomad4 SAS exome AF: 0.893

Gnomad4 FIN exome AF: 0.767

Gnomad4 NFE exome AF: 0.843

Gnomad4 OTH exome AF: 0.821

GnomAD4 genome AF: 0.821 AC: 124915 AN: 152180 Hom.: 51774 Cov.: 32 AF XY: 0.816 AC XY: 60736 AN XY: 74402

Gnomad4 AFR AF: 0.869

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.841

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.887

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.822

Alfa AF: 0.789 Hom.: 2402

Bravo AF: 0.814

Asia WGS AF: 0.758 AC: 2637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.36

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: rs752307; hg19: chr1-226551529; COSMIC: COSV64689696; COSMIC: COSV64689696;