1-226390398-T-C

Position:

• chr1-226390398-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001618.4(PARP1):​c.617+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 1,611,530 control chromosomes in the GnomAD database, including 506,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.83 (53472 hom., cov: 31)
  • Exomes 𝑓: 0.79 (452661 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.75

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]

PARP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-226390398-T-C is Benign according to our data. Variant chr1-226390398-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP1	NM_001618.4	c.617+12A>G		intron_variant		ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.617+12A>G		intron_variant		1	NM_001618.4	ENSP00000355759.5

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126790 AN: 152022 Hom.: 53408 Cov.: 31

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.804

GnomAD3 exomes AF: 0.810 AC: 203319 AN: 251036 Hom.: 83146 AF XY: 0.800 AC XY: 108525 AN XY: 135708

Gnomad AFR exome AF: 0.941

Gnomad AMR exome AF: 0.870

Gnomad ASJ exome AF: 0.719

Gnomad EAS exome AF: 0.939

Gnomad SAS exome AF: 0.739

Gnomad FIN exome AF: 0.880

Gnomad NFE exome AF: 0.768

Gnomad OTH exome AF: 0.775

GnomAD4 exome AF: 0.786 AC: 1146982 AN: 1459390 Hom.: 452661 Cov.: 39 AF XY: 0.783 AC XY: 568479 AN XY: 726040

Gnomad4 AFR exome AF: 0.945

Gnomad4 AMR exome AF: 0.861

Gnomad4 ASJ exome AF: 0.709

Gnomad4 EAS exome AF: 0.934

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 0.873

Gnomad4 NFE exome AF: 0.774

Gnomad4 OTH exome AF: 0.785

GnomAD4 genome AF: 0.834 AC: 126914 AN: 152140 Hom.: 53472 Cov.: 31 AF XY: 0.839 AC XY: 62416 AN XY: 74390

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.940

Gnomad4 SAS AF: 0.753

Gnomad4 FIN AF: 0.878

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.806

Alfa AF: 0.787 Hom.: 8714

Bravo AF: 0.835

Asia WGS AF: 0.856 AC: 2977 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.028
DANN	Benign	0.33

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: rs1805403; hg19: chr1-226578099;