rs2271347

chr1-226361797-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.2963+172C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 683,664 control chromosomes in the GnomAD database, including 15,147 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 0.16 (2599 hom., cov: 31)
  • Exomes 𝑓: 0.21 (12548 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP1	NM_001618.4	c.2963+172C>T		intron_variant		ENST00000366794.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP1	ENST00000366794.10	c.2963+172C>T		intron_variant		1	NM_001618.4	P1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25033 AN: 151984 Hom.: 2600 Cov.: 31

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.0596

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.206 AC: 109499 AN: 531562 Hom.: 12548 Cov.: 5 AF XY: 0.212 AC XY: 60483 AN XY: 285518

Gnomad4 AFR exome AF: 0.0609

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.0665

Gnomad4 SAS exome AF: 0.257

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.165 AC: 25025 AN: 152102 Hom.: 2599 Cov.: 31 AF XY: 0.160 AC XY: 11860 AN XY: 74350

Gnomad4 AFR AF: 0.0607

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.0597

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.193

Alfa AF: 0.221 Hom.: 3099

Bravo AF: 0.163

Asia WGS AF: 0.145 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.43
Dann	Benign	0.24

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: rs2271347; hg19: chr1-226549498;