1-226376990-T-C

Variant names:

• chr1-226376990-T-C
• rs3219090
• NM_001618.4:c.1941+118A>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.1941+118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 924,618 control chromosomes in the GnomAD database, including 182,375 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 0.58 (26303 hom., cov: 31)
  • Exomes 𝑓: 0.62 (156072 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 61 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001618.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP1	NM_001618.4	MANE Select	c.1941+118A>G		intron	N/A	NP_001609.2	P09874

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP1	ENST00000366794.10	TSL:1 MANE Select	c.1941+118A>G		intron	N/A	ENSP00000355759.5	P09874
	PARP1	ENST00000922077.1		c.1935+118A>G		intron	N/A	ENSP00000592136.1
	PARP1	ENST00000922078.1		c.1935+118A>G		intron	N/A	ENSP00000592137.1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87487 AN: 151796 Hom.: 26306 Cov.: 31

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.625 AC: 482689 AN: 772704 Hom.: 156072 AF XY: 0.628 AC XY: 255283 AN XY: 406252

African (AFR) AF: 0.439 AC: 8512 AN: 19400

American (AMR) AF: 0.465 AC: 18405 AN: 39604

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 14441 AN: 20884

East Asian (EAS) AF: 0.208 AC: 7527 AN: 36202

South Asian (SAS) AF: 0.638 AC: 43825 AN: 68704

European-Finnish (FIN) AF: 0.598 AC: 30974 AN: 51794

Middle Eastern (MID) AF: 0.647 AC: 1802 AN: 2786

European-Non Finnish (NFE) AF: 0.674 AC: 334228 AN: 496216

Other (OTH) AF: 0.619 AC: 22975 AN: 37114

GnomAD4 genome AF: 0.576 AC: 87512 AN: 151914 Hom.: 26303 Cov.: 31 AF XY: 0.572 AC XY: 42463 AN XY: 74230

African (AFR) AF: 0.451 AC: 18679 AN: 41394

American (AMR) AF: 0.543 AC: 8280 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2408 AN: 3470

East Asian (EAS) AF: 0.193 AC: 999 AN: 5172

South Asian (SAS) AF: 0.627 AC: 3021 AN: 4816

European-Finnish (FIN) AF: 0.600 AC: 6324 AN: 10542

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45607 AN: 67946

Other (OTH) AF: 0.606 AC: 1279 AN: 2110

Alfa AF: 0.635 Hom.: 142031

Bravo AF: 0.562

Asia WGS AF: 0.459 AC: 1596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.7
DANN	Benign	0.78
PhyloP100		1.3
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: rs3219090; hg19: chr1-226564691; COSMIC: COSV64689321;