rs2117114

chr1-226383918-G-Achr1-226383918-G-C

Variant summary

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

The NM_001618.4(PARP1):c.1012-735C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,190 control chromosomes in the GnomAD database, including 51,256 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 (51256 hom., cov: 33)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP1	NM_001618.4	c.1012-735C>T		intron_variant		ENST00000366794.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP1	ENST00000366794.10	c.1012-735C>T		intron_variant		1	NM_001618.4	P1

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124184 AN: 152072 Hom.: 51244 Cov.: 33

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.820

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

GnomAD4 genome AF: 0.816 AC: 124243 AN: 152190 Hom.: 51256 Cov.: 33 AF XY: 0.810 AC XY: 60304 AN XY: 74420

Gnomad4 AFR AF: 0.869

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.832

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.803

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.817

Alfa AF: 0.809 Hom.: 8104

Bravo AF: 0.811

Asia WGS AF: 0.703 AC: 2445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.10
Dann	Benign	0.39

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: rs2117114; hg19: chr1-226571619;