rs3219123

Positions:

• chr1-226367647-G-A
• chr1-226367647-G-T

Variant summary

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

The NM_001618.4(PARP1):​c.2278-39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0511 in 1,611,774 control chromosomes in the GnomAD database, including 2,511 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 0.040 (197 hom., cov: 32)
  • Exomes 𝑓: 0.052 (2314 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489

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 = 0.058 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP1	NM_001618.4	c.2278-39C>T		intron_variant		ENST00000366794.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP1	ENST00000366794.10	c.2278-39C>T		intron_variant		1	NM_001618.4	P1

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6129 AN: 152156 Hom.: 198 Cov.: 32

Gnomad AFR AF: 0.00965

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0850

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.0375

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0595

Gnomad OTH AF: 0.0498

GnomAD3 exomes AF: 0.0445 AC: 11130 AN: 250192 Hom.: 337 AF XY: 0.0466 AC XY: 6309 AN XY: 135332

Gnomad AFR exome AF: 0.00862

Gnomad AMR exome AF: 0.0237

Gnomad ASJ exome AF: 0.0900

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0452

Gnomad FIN exome AF: 0.0354

Gnomad NFE exome AF: 0.0601

Gnomad OTH exome AF: 0.0512

GnomAD4 exome AF: 0.0522 AC: 76245 AN: 1459500 Hom.: 2314 Cov.: 32 AF XY: 0.0529 AC XY: 38394 AN XY: 726196

Gnomad4 AFR exome AF: 0.00720

Gnomad4 AMR exome AF: 0.0259

Gnomad4 ASJ exome AF: 0.0901

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.0469

Gnomad4 FIN exome AF: 0.0357

Gnomad4 NFE exome AF: 0.0564

Gnomad4 OTH exome AF: 0.0557

GnomAD4 genome AF: 0.0402 AC: 6128 AN: 152274 Hom.: 197 Cov.: 32 AF XY: 0.0390 AC XY: 2903 AN XY: 74472

Gnomad4 AFR AF: 0.00963

Gnomad4 AMR AF: 0.0406

Gnomad4 ASJ AF: 0.0850

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0467

Gnomad4 FIN AF: 0.0375

Gnomad4 NFE AF: 0.0595

Gnomad4 OTH AF: 0.0492

Alfa AF: 0.0564 Hom.: 96

Bravo AF: 0.0385

Asia WGS AF: 0.0200 AC: 71 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	1.5
DANN	Benign	0.50

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: rs3219123; hg19: chr1-226555348;