rs1805404

chr1-226402257-G-Achr1-226402257-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001618.4(PARP1):c.243C>T(p.Asp81=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,614,006 control chromosomes in the GnomAD database, including 27,930 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 0.18 (2956 hom., cov: 33)
  • Exomes 𝑓: 0.17 (24974 hom.)
• Consequence: PARP1 NM_001618.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=3.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP1	NM_001618.4	c.243C>T	p.Asp81=	synonymous_variant	2/23	ENST00000366794.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP1	ENST00000366794.10	c.243C>T	p.Asp81=	synonymous_variant	2/23	1	NM_001618.4	P1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27223 AN: 152084 Hom.: 2944 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.177

GnomAD3 exomes AF: 0.218 AC: 54895 AN: 251372 Hom.: 7918 AF XY: 0.204 AC XY: 27728 AN XY: 135868

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.426

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.448

Gnomad SAS exome AF: 0.103

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.171 AC: 250468 AN: 1461804 Hom.: 24974 Cov.: 34 AF XY: 0.168 AC XY: 122451 AN XY: 727214

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.421

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.179 AC: 27278 AN: 152202 Hom.: 2956 Cov.: 33 AF XY: 0.184 AC XY: 13676 AN XY: 74412

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.178

Alfa AF: 0.145 Hom.: 975

Bravo AF: 0.186

Asia WGS AF: 0.242 AC: 842 AN: 3478

EpiCase AF: 0.149

EpiControl AF: 0.155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	10
Dann	Benign	0.49
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.8

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: rs1805404; hg19: chr1-226589958; COSMIC: COSV64687027;