1-226390346-G-T

Position:

• chr1-226390346-G-T

Variant summary

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

The ENST00000366794.10(PARP1):​c.617+64C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,385,860 control chromosomes in the GnomAD database, including 24,831 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 0.17 (2810 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22021 hom.)
• Consequence: PARP1 ENST00000366794.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP1	NM_001618.4	c.617+64C>A		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+64C>A		intron_variant		1	NM_001618.4	ENSP00000355759	P1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26156 AN: 151992 Hom.: 2801 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.172

GnomAD4 exome AF: 0.174 AC: 214229 AN: 1233750 Hom.: 22021 AF XY: 0.170 AC XY: 106210 AN XY: 624840

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.420

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.172 AC: 26197 AN: 152110 Hom.: 2810 Cov.: 32 AF XY: 0.177 AC XY: 13167 AN XY: 74354

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.173

Alfa AF: 0.153 Hom.: 2509

Bravo AF: 0.178

Asia WGS AF: 0.234 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.43
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: rs1805411; hg19: chr1-226578047; COSMIC: COSV64688261; COSMIC: COSV64688261;