chr1-226407946-C-G

Position:

• chr1-226407946-C-G

Variant summary

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

The ENST00000366794.10(PARP1):​c.-17G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,610,132 control chromosomes in the GnomAD database, including 28,309 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 (2730 hom., cov: 32)
  • Exomes 𝑓: 0.17 (25579 hom.)
• Consequence: PARP1 ENST00000366794.10 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.951

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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP1	NM_001618.4	c.-17G>C		5_prime_UTR_variant	1/23	ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.-17G>C		5_prime_UTR_variant	1/23	1	NM_001618.4	ENSP00000355759	P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24523 AN: 151984 Hom.: 2724 Cov.: 32

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.169

GnomAD3 exomes AF: 0.214 AC: 52583 AN: 246266 Hom.: 7562 AF XY: 0.201 AC XY: 26841 AN XY: 133850

Gnomad AFR exome AF: 0.0465

Gnomad AMR exome AF: 0.418

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.443

Gnomad SAS exome AF: 0.102

Gnomad FIN exome AF: 0.261

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.173 AC: 252465 AN: 1458040 Hom.: 25579 Cov.: 35 AF XY: 0.170 AC XY: 123645 AN XY: 725378

Gnomad4 AFR exome AF: 0.0483

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.420

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.263

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.161 AC: 24545 AN: 152092 Hom.: 2730 Cov.: 32 AF XY: 0.168 AC XY: 12516 AN XY: 74376

Gnomad4 AFR AF: 0.0539

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.170

Alfa AF: 0.159 Hom.: 387

Bravo AF: 0.164

Asia WGS AF: 0.226 AC: 782 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.70
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		3.2

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: rs907187; hg19: chr1-226595647; COSMIC: COSV64687065; COSMIC: COSV64687065;