rs8679

Positions:

• chr1-226360853-A-G

Variant summary

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

The NM_001618.4(PARP1):​c.*607T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 227,816 control chromosomes in the GnomAD database, including 4,488 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 (2638 hom., cov: 31)
  • Exomes 𝑓: 0.21 (1850 hom.)
• Consequence: PARP1 NM_001618.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP1	NM_001618.4	c.*607T>C		3_prime_UTR_variant	23/23	ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.*607T>C		3_prime_UTR_variant	23/23	1	NM_001618.4	ENSP00000355759	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25230 AN: 152106 Hom.: 2639 Cov.: 31

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.0595

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.197

GnomAD4 exome AF: 0.206 AC: 15609 AN: 75592 Hom.: 1850 Cov.: 0 AF XY: 0.211 AC XY: 7347 AN XY: 34902

Gnomad4 AFR exome AF: 0.0567

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.0648

Gnomad4 SAS exome AF: 0.269

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.166 AC: 25223 AN: 152224 Hom.: 2638 Cov.: 31 AF XY: 0.161 AC XY: 11968 AN XY: 74428

Gnomad4 AFR AF: 0.0608

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.0596

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.195

Alfa AF: 0.220 Hom.: 3938

Bravo AF: 0.165

Asia WGS AF: 0.145 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.80
DANN	Benign	0.63

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: rs8679; hg19: chr1-226548554;