1-226402008-C-T

Variant names:

• chr1-226402008-C-T
• rs2666428
• NM_001618.4:c.286+206G>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.286+206G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,485,744 control chromosomes in the GnomAD database, including 105,456 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 0.44 (16357 hom., cov: 33)
  • Exomes 𝑓: 0.35 (89099 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.593
• Publications: 22 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=-0.81).
• 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.286+206G>A		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.286+206G>A		intron_variant	Intron 2 of 22	1	NM_001618.4	ENSP00000355759.5

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67170 AN: 151890 Hom.: 16327 Cov.: 33

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.404

GnomAD2 exomes AF: 0.429 AC: 46898 AN: 109316 AF XY: 0.418

Gnomad AFR exome AF: 0.628

Gnomad AMR exome AF: 0.520

Gnomad ASJ exome AF: 0.312

Gnomad EAS exome AF: 0.816

Gnomad FIN exome AF: 0.406

Gnomad NFE exome AF: 0.320

Gnomad OTH exome AF: 0.379

GnomAD4 exome AF: 0.352 AC: 469959 AN: 1333736 Hom.: 89099 Cov.: 33 AF XY: 0.352 AC XY: 228467 AN XY: 649880

African (AFR) AF: 0.628 AC: 18457 AN: 29368

American (AMR) AF: 0.505 AC: 13024 AN: 25774

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 6617 AN: 21602

East Asian (EAS) AF: 0.793 AC: 27704 AN: 34936

South Asian (SAS) AF: 0.366 AC: 25318 AN: 69224

European-Finnish (FIN) AF: 0.401 AC: 18391 AN: 45832

Middle Eastern (MID) AF: 0.335 AC: 1801 AN: 5378

European-Non Finnish (NFE) AF: 0.323 AC: 337901 AN: 1046460

Other (OTH) AF: 0.376 AC: 20746 AN: 55162

GnomAD4 genome AF: 0.443 AC: 67264 AN: 152008 Hom.: 16357 Cov.: 33 AF XY: 0.446 AC XY: 33150 AN XY: 74310

African (AFR) AF: 0.613 AC: 25388 AN: 41422

American (AMR) AF: 0.462 AC: 7063 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1072 AN: 3470

East Asian (EAS) AF: 0.806 AC: 4177 AN: 5180

South Asian (SAS) AF: 0.376 AC: 1815 AN: 4822

European-Finnish (FIN) AF: 0.400 AC: 4218 AN: 10552

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22384 AN: 67960

Other (OTH) AF: 0.404 AC: 854 AN: 2114

Alfa AF: 0.358 Hom.: 13857

Bravo AF: 0.459

Asia WGS AF: 0.548 AC: 1908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.73
PhyloP100		-0.59
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: rs2666428; hg19: chr1-226589709;