dbSNP rs2280712: PARP1:c.287-78G>A (chr1-226392392-C-T) – 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.287-78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 954,124 control chromosomes in the GnomAD database, including 13,768 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 0.13 ( 1763 hom., cov: 32)

Exomes 𝑓: 0.16 ( 12005 hom. )

Consequence

PARP1
NM_001618.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.18

Publications

9 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=-0.7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP1	NM_001618.4 link	c.287-78G>A		intron_variant	Intron 2 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.287-78G>A		intron_variant	Intron 2 of 22	1	NM_001618.4	ENSP00000355759.5		P09874

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20553

AN:

152098

Hom.:

1766

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0519

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.162

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.138

GnomAD4 exome

AF:

0.163

AC:

131056

AN:

801908

Hom.:

12005

AF XY:

0.166

AC XY:

70598

AN XY:

425508

show subpopulations

African (AFR)

AF:

0.0499

AC:

1060

AN:

21230

American (AMR)

AF:

0.110

AC:

4796

AN:

43788

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

3149

AN:

22036

East Asian (EAS)

AF:

0.325

AC:

11923

AN:

36672

South Asian (SAS)

AF:

0.180

AC:

13167

AN:

73022

European-Finnish (FIN)

AF:

0.167

AC:

8332

AN:

49994

Middle Eastern (MID)

AF:

0.168

AC:

509

AN:

3038

European-Non Finnish (NFE)

AF:

0.159

AC:

81826

AN:

513542

Other (OTH)

AF:

0.163

AC:

6294

AN:

38586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

5265

10530

15795

21060

26325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1564

3128

4692

6256

7820

<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:

0.135

AC:

20536

AN:

152216

Hom.:

1763

Cov.:

AF XY:

0.137

AC XY:

10160

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0518

AC:

2151

AN:

41556

American (AMR)

AF:

0.107

AC:

1637

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

480

AN:

3470

East Asian (EAS)

AF:

0.337

AC:

1741

AN:

5172

South Asian (SAS)

AF:

0.179

AC:

861

AN:

4822

European-Finnish (FIN)

AF:

0.166

AC:

1763

AN:

10594

Middle Eastern (MID)

AF:

0.161

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.168

AC:

11438

AN:

67998

Other (OTH)

AF:

0.136

AC:

287

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

886

1772

2657

3543

4429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<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:

0.156

Hom.:

1237

Bravo

AF:

0.129

Asia WGS

AF:

0.230

AC:

801

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.84

(source)

DANN

Benign

0.87

PhyloP100

-2.2

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