chr1-226364367-G-A

Variant names:

• chr1-226364367-G-A
• rs3219142
• NM_001618.4:c.2659-297C>T

Variant summary

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

The NM_001618.4(PARP1):​c.2659-297C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 386,900 control chromosomes in the GnomAD database, including 5,762 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 0.14 (2032 hom., cov: 32)
  • Exomes 𝑓: 0.16 (3730 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610

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 (NFE) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP1	NM_001618.4	c.2659-297C>T		intron_variant	Intron 19 of 22	ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.2659-297C>T		intron_variant	Intron 19 of 22	1	NM_001618.4	ENSP00000355759.5

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21708 AN: 152030 Hom.: 2030 Cov.: 32

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.0857

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.135

GnomAD4 exome AF: 0.165 AC: 38698 AN: 234752 Hom.: 3730 Cov.: 0 AF XY: 0.157 AC XY: 19749 AN XY: 126190

Gnomad4 AFR exome AF: 0.0359

Gnomad4 AMR exome AF: 0.196

Gnomad4 ASJ exome AF: 0.238

Gnomad4 EAS exome AF: 0.0346

Gnomad4 SAS exome AF: 0.0933

Gnomad4 FIN exome AF: 0.204

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.143 AC: 21704 AN: 152148 Hom.: 2032 Cov.: 32 AF XY: 0.143 AC XY: 10626 AN XY: 74376

Gnomad4 AFR AF: 0.0374

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.0330

Gnomad4 SAS AF: 0.0853

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.134

Alfa AF: 0.177 Hom.: 900

Bravo AF: 0.135

Asia WGS AF: 0.0610 AC: 210 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	4.3
DANN	Benign	0.68

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: rs3219142; hg19: chr1-226552068;