rs2048426

Variant names:

• chr1-226406600-C-T
• rs2048426
• NM_001618.4:c.120+1210G>A

Variant summary

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

The NM_001618.4(PARP1):​c.120+1210G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 152,034 control chromosomes in the GnomAD database, including 16,629 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 0.45 (16629 hom., cov: 32)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14
• Publications: 7 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=-0.85).
• 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.120+1210G>A		intron_variant	Intron 1 of 22	ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.120+1210G>A		intron_variant	Intron 1 of 22	1	NM_001618.4	ENSP00000355759.5

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67870 AN: 151916 Hom.: 16599 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.447 AC: 67964 AN: 152034 Hom.: 16629 Cov.: 32 AF XY: 0.452 AC XY: 33576 AN XY: 74336

African (AFR) AF: 0.614 AC: 25418 AN: 41428

American (AMR) AF: 0.464 AC: 7093 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1081 AN: 3470

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

South Asian (SAS) AF: 0.378 AC: 1821 AN: 4818

European-Finnish (FIN) AF: 0.430 AC: 4554 AN: 10580

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.334 AC: 22669 AN: 67956

Other (OTH) AF: 0.408 AC: 863 AN: 2114

Alfa AF: 0.392 Hom.: 1549

Bravo AF: 0.462

Asia WGS AF: 0.548 AC: 1909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.83
DANN	Benign	0.70
PhyloP100		-3.1
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: rs2048426; hg19: chr1-226594301;