rs2027440

Variant names:

• chr1-226376158-C-T
• rs2027440
• NM_001618.4:c.1941+950G>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.1941+950G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,038 control chromosomes in the GnomAD database, including 51,210 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 0.82 (51210 hom., cov: 31)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• Publications: 18 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP1	NM_001618.4	c.1941+950G>A		intron_variant	Intron 13 of 22	ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.1941+950G>A		intron_variant	Intron 13 of 22	1	NM_001618.4	ENSP00000355759.5

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124061 AN: 151920 Hom.: 51198 Cov.: 31

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.833

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.820

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

GnomAD4 genome AF: 0.816 AC: 124120 AN: 152038 Hom.: 51210 Cov.: 31 AF XY: 0.810 AC XY: 60198 AN XY: 74286

African (AFR) AF: 0.869 AC: 36028 AN: 41476

American (AMR) AF: 0.690 AC: 10516 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 2889 AN: 3470

East Asian (EAS) AF: 0.533 AC: 2751 AN: 5162

South Asian (SAS) AF: 0.804 AC: 3862 AN: 4806

European-Finnish (FIN) AF: 0.767 AC: 8110 AN: 10570

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57138 AN: 67988

Other (OTH) AF: 0.818 AC: 1725 AN: 2110

Alfa AF: 0.831 Hom.: 26618

Bravo AF: 0.811

Asia WGS AF: 0.703 AC: 2444 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.40
PhyloP100		-0.061
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: rs2027440; hg19: chr1-226563859; COSMIC: COSV64689722;