rs1805410

Positions:

• chr1-226380964-T-C

Variant summary

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

The NM_001618.4(PARP1):​c.1300+104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,283,754 control chromosomes in the GnomAD database, including 15,711 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 0.13 (1464 hom., cov: 33)
  • Exomes 𝑓: 0.15 (14247 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP1	NM_001618.4	c.1300+104A>G		intron_variant		ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.1300+104A>G		intron_variant		1	NM_001618.4	ENSP00000355759	P1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20113 AN: 152058 Hom.: 1465 Cov.: 33

Gnomad AFR AF: 0.0962

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0887

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.153 AC: 172733 AN: 1131578 Hom.: 14247 AF XY: 0.155 AC XY: 89259 AN XY: 576800

Gnomad4 AFR exome AF: 0.0968

Gnomad4 AMR exome AF: 0.0808

Gnomad4 ASJ exome AF: 0.0964

Gnomad4 EAS exome AF: 0.0404

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.148

GnomAD4 genome AF: 0.132 AC: 20132 AN: 152176 Hom.: 1464 Cov.: 33 AF XY: 0.133 AC XY: 9894 AN XY: 74392

Gnomad4 AFR AF: 0.0962

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0887

Gnomad4 EAS AF: 0.0313

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.159

Alfa AF: 0.150 Hom.: 2495

Bravo AF: 0.125

Asia WGS AF: 0.161 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.28

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: rs1805410; hg19: chr1-226568665; COSMIC: COSV64689744;