rs2048424

Variant names:

• chr1-226395306-G-C
• rs2048424
• NM_001618.4:c.287-2992C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001618.4(PARP1):​c.287-2992C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 151,916 control chromosomes in the GnomAD database, including 14,587 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 0.42 (14587 hom., cov: 31)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646
• Publications: 8 publications found

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]

PARP1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP1	NM_001618.4	c.287-2992C>G		intron_variant	Intron 2 of 22	ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.287-2992C>G		intron_variant	Intron 2 of 22	1	NM_001618.4	ENSP00000355759.5

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64048 AN: 151804 Hom.: 14557 Cov.: 31

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.394

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.422 AC: 64137 AN: 151916 Hom.: 14587 Cov.: 31 AF XY: 0.426 AC XY: 31654 AN XY: 74244

African (AFR) AF: 0.542 AC: 22469 AN: 41426

American (AMR) AF: 0.456 AC: 6971 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1062 AN: 3466

East Asian (EAS) AF: 0.807 AC: 4172 AN: 5172

South Asian (SAS) AF: 0.373 AC: 1792 AN: 4806

European-Finnish (FIN) AF: 0.399 AC: 4199 AN: 10516

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22354 AN: 67936

Other (OTH) AF: 0.393 AC: 830 AN: 2110

Alfa AF: 0.375 Hom.: 1392

Bravo AF: 0.436

Asia WGS AF: 0.543 AC: 1887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.49
DANN	Benign	0.42
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2048424; hg19: chr1-226583007;