rs3219090

chr1-226376990-T-C

Variant summary

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

The NM_001618.4(PARP1):c.1941+118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 924,618 control chromosomes in the GnomAD database, including 182,375 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 0.58 (26303 hom., cov: 31)
  • Exomes 𝑓: 0.62 (156072 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP1	NM_001618.4	c.1941+118A>G		intron_variant		ENST00000366794.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP1	ENST00000366794.10	c.1941+118A>G		intron_variant		1	NM_001618.4	P1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87487 AN: 151796 Hom.: 26306 Cov.: 31

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.625 AC: 482689 AN: 772704 Hom.: 156072 AF XY: 0.628 AC XY: 255283 AN XY: 406252

Gnomad4 AFR exome AF: 0.439

Gnomad4 AMR exome AF: 0.465

Gnomad4 ASJ exome AF: 0.691

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.638

Gnomad4 FIN exome AF: 0.598

Gnomad4 NFE exome AF: 0.674

Gnomad4 OTH exome AF: 0.619

GnomAD4 genome AF: 0.576 AC: 87512 AN: 151914 Hom.: 26303 Cov.: 31 AF XY: 0.572 AC XY: 42463 AN XY: 74230

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.606

Alfa AF: 0.650 Hom.: 71991

Bravo AF: 0.562

Asia WGS AF: 0.459 AC: 1596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.7
Dann	Benign	0.78

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: rs3219090; hg19: chr1-226564691; COSMIC: COSV64689321;