Genetic Variant PARP1:c.2786+115G>C (chr1-226363828-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001618.4(PARP1):c.2786+115G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 1,048,236 control chromosomes in the GnomAD database, including 356,254 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 ( 51774 hom., cov: 32)

Exomes 𝑓: 0.82 ( 304480 hom. )

Consequence

PARP1
NM_001618.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.792

Publications

19 publications found

Variant links:

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

PARP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP1	NM_001618.4 link	c.2786+115G>C		intron_variant	Intron 20 of 22	ENST00000366794.10	NP_001609.2	P09874A0A024R3T8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10 link	c.2786+115G>C		intron_variant	Intron 20 of 22	1	NM_001618.4	ENSP00000355759.5		P09874

Frequencies

GnomAD3 genomes

AF:

0.821

AC:

124852

AN:

152062

Hom.:

51758

Cov.:

show subpopulations

Gnomad AFR

AF:

0.870

Gnomad AMI

AF:

0.928

Gnomad AMR

AF:

0.692

Gnomad ASJ

AF:

0.841

Gnomad EAS

AF:

0.570

Gnomad SAS

AF:

0.887

Gnomad FIN

AF:

0.767

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.841

Gnomad OTH

AF:

0.823

GnomAD4 exome

AF:

0.820

AC:

734809

AN:

896056

Hom.:

304480

AF XY:

0.826

AC XY:

385296

AN XY:

466740

show subpopulations

African (AFR)

AF:

0.872

AC:

19694

AN:

22586

American (AMR)

AF:

0.593

AC:

25104

AN:

42324

Ashkenazi Jewish (ASJ)

AF:

0.844

AC:

18836

AN:

22328

East Asian (EAS)

AF:

0.582

AC:

21280

AN:

36546

South Asian (SAS)

AF:

0.893

AC:

65421

AN:

73286

European-Finnish (FIN)

AF:

0.767

AC:

38874

AN:

50682

Middle Eastern (MID)

AF:

0.835

AC:

2558

AN:

3062

European-Non Finnish (NFE)

AF:

0.843

AC:

509293

AN:

604142

Other (OTH)

AF:

0.821

AC:

33749

AN:

41100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

6241

12482

18723

24964

31205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8092

16184

24276

32368

40460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.821

AC:

124915

AN:

152180

Hom.:

51774

Cov.:

AF XY:

0.816

AC XY:

60736

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.869

AC:

36089

AN:

41518

American (AMR)

AF:

0.691

AC:

10553

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.841

AC:

2918

AN:

3468

East Asian (EAS)

AF:

0.571

AC:

2950

AN:

5170

South Asian (SAS)

AF:

0.887

AC:

4280

AN:

4826

European-Finnish (FIN)

AF:

0.767

AC:

8113

AN:

10582

Middle Eastern (MID)

AF:

0.867

AC:

255

AN:

294

European-Non Finnish (NFE)

AF:

0.841

AC:

57173

AN:

68022

Other (OTH)

AF:

0.822

AC:

1738

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1107

2215

3322

4430

5537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.789

Hom.:

2402

Bravo

AF:

0.814

Asia WGS

AF:

0.758

AC:

2637

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.47

(source)

DANN

Benign

0.36

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over