rs3219149

Positions:

• chr1-226360716-C-A
• chr1-226360716-C-T

Variant summary

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

The NM_001618.4(PARP1):​c.*744G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 223,584 control chromosomes in the GnomAD database, including 121 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 0.011 (96 hom., cov: 31)
  • Exomes 𝑓: 0.010 (25 hom.)
• Consequence: PARP1 NM_001618.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12

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=-0.49).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP1	NM_001618.4	c.*744G>T		3_prime_UTR_variant	23/23	ENST00000366794.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP1	ENST00000366794.10	c.*744G>T		3_prime_UTR_variant	23/23	1	NM_001618.4	P1

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1715 AN: 152102 Hom.: 94 Cov.: 31

Gnomad AFR AF: 0.00203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0328

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000661

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0173

GnomAD4 exome AF: 0.0103 AC: 735 AN: 71364 Hom.: 25 Cov.: 0 AF XY: 0.00959 AC XY: 316 AN XY: 32938

Gnomad4 AFR exome AF: 0.00210

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0424

Gnomad4 SAS exome AF: 0.00162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000522

Gnomad4 OTH exome AF: 0.00770

GnomAD4 genome AF: 0.0113 AC: 1721 AN: 152220 Hom.: 96 Cov.: 31 AF XY: 0.0129 AC XY: 957 AN XY: 74434

Gnomad4 AFR AF: 0.00202

Gnomad4 AMR AF: 0.0894

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0329

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.000661

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.00142 Hom.: 0

Bravo AF: 0.0207

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.060
DANN	Benign	0.80

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: rs3219149; hg19: chr1-226548417;