dbSNP rs747657: PARP1:c.2787-63C>G (chr1-226363223-G-C) – 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.2787-63C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,072,544 control chromosomes in the GnomAD database, including 214,043 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 ( 26425 hom., cov: 32)

Exomes 𝑓: 0.63 ( 187618 hom. )

Consequence

PARP1
NM_001618.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.616

Publications

14 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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP1	NM_001618.4 link	c.2787-63C>G		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.2787-63C>G		intron_variant	Intron 20 of 22	1	NM_001618.4	ENSP00000355759.5		P09874

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87768

AN:

151954

Hom.:

26426

Cov.:

show subpopulations

Gnomad AFR

AF:

0.457

Gnomad AMI

AF:

0.787

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.693

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.626

Gnomad FIN

AF:

0.601

Gnomad MID

AF:

0.680

Gnomad NFE

AF:

0.671

Gnomad OTH

AF:

0.606

GnomAD4 exome

AF:

0.629

AC:

578578

AN:

920472

Hom.:

187618

AF XY:

0.632

AC XY:

304304

AN XY:

481414

show subpopulations

African (AFR)

AF:

0.441

AC:

10181

AN:

23094

American (AMR)

AF:

0.463

AC:

20378

AN:

43984

Ashkenazi Jewish (ASJ)

AF:

0.690

AC:

15719

AN:

22792

East Asian (EAS)

AF:

0.207

AC:

7727

AN:

37300

South Asian (SAS)

AF:

0.637

AC:

47905

AN:

75212

European-Finnish (FIN)

AF:

0.598

AC:

31667

AN:

52976

Middle Eastern (MID)

AF:

0.669

AC:

3118

AN:

4658

European-Non Finnish (NFE)

AF:

0.672

AC:

415488

AN:

617854

Other (OTH)

AF:

0.620

AC:

26395

AN:

42602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

11548

23096

34644

46192

57740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7428

14856

22284

29712

37140

<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:

0.577

AC:

87799

AN:

152072

Hom.:

26425

Cov.:

AF XY:

0.573

AC XY:

42630

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.456

AC:

18920

AN:

41476

American (AMR)

AF:

0.543

AC:

8302

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.693

AC:

2402

AN:

3466

East Asian (EAS)

AF:

0.194

AC:

1003

AN:

5170

South Asian (SAS)

AF:

0.626

AC:

3020

AN:

4822

European-Finnish (FIN)

AF:

0.601

AC:

6346

AN:

10556

Middle Eastern (MID)

AF:

0.687

AC:

202

AN:

294

European-Non Finnish (NFE)

AF:

0.671

AC:

45615

AN:

67994

Other (OTH)

AF:

0.606

AC:

1276

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1862

3724

5585

7447

9309

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

748

1496

2244

2992

3740

<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:

0.625

Hom.:

3770

Bravo

AF:

0.563

Asia WGS

AF:

0.459

AC:

1597

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.47

(source)

DANN

Benign

0.66

PhyloP100

-0.62

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