rs1805413

Positions:

• chr1-226368136-G-A

Variant summary

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

The NM_001618.4(PARP1):​c.2277+63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00461 in 1,606,440 control chromosomes in the GnomAD database, including 265 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 0.0065 (28 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (237 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP1	NM_001618.4	c.2277+63C>T		intron_variant		ENST00000366794.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP1	ENST00000366794.10	c.2277+63C>T		intron_variant		1	NM_001618.4	P1

Frequencies

GnomAD3 genomes AF: 0.00646 AC: 983 AN: 152188 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.0960

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00148

Gnomad OTH AF: 0.00812

GnomAD4 exome AF: 0.00441 AC: 6419 AN: 1454134 Hom.: 237 AF XY: 0.00425 AC XY: 3074 AN XY: 723832

Gnomad4 AFR exome AF: 0.000330

Gnomad4 AMR exome AF: 0.000895

Gnomad4 ASJ exome AF: 0.00211

Gnomad4 EAS exome AF: 0.0921

Gnomad4 SAS exome AF: 0.00317

Gnomad4 FIN exome AF: 0.0240

Gnomad4 NFE exome AF: 0.000554

Gnomad4 OTH exome AF: 0.00880

GnomAD4 genome AF: 0.00646 AC: 984 AN: 152306 Hom.: 28 Cov.: 32 AF XY: 0.00744 AC XY: 554 AN XY: 74464

Gnomad4 AFR AF: 0.000577

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.0962

Gnomad4 SAS AF: 0.00435

Gnomad4 FIN AF: 0.0248

Gnomad4 NFE AF: 0.00148

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00513 Hom.: 1

Bravo AF: 0.00502

Asia WGS AF: 0.0490 AC: 169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.054
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1805413; hg19: chr1-226555837; COSMIC: COSV64689630; COSMIC: COSV64689630;