Genetic Variant PARP1:c.617+64C>A (chr1-226390346-G-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.617+64C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,385,860 control chromosomes in the GnomAD database, including 24,831 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 0.17 ( 2810 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22021 hom. )

Consequence

PARP1
NM_001618.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.132

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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 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.617+64C>A		intron	N/A	NP_001609.2	P09874

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PARP1	ENST00000366794.10	TSL:1 MANE Select	c.617+64C>A	intron	N/A	ENSP00000355759.5	P09874
PARP1	ENST00000922077.1		c.611+64C>A	intron	N/A	ENSP00000592136.1
PARP1	ENST00000922078.1		c.611+64C>A	intron	N/A	ENSP00000592137.1

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26156

AN:

151992

Hom.:

2801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.172

GnomAD4 exome

AF:

0.174

AC:

214229

AN:

1233750

Hom.:

22021

AF XY:

0.170

AC XY:

106210

AN XY:

624840

show subpopulations

African (AFR)

AF:

0.102

AC:

2959

AN:

28950

American (AMR)

AF:

0.405

AC:

17942

AN:

44338

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

3852

AN:

24708

East Asian (EAS)

AF:

0.420

AC:

16231

AN:

38652

South Asian (SAS)

AF:

0.107

AC:

8725

AN:

81384

European-Finnish (FIN)

AF:

0.234

AC:

12377

AN:

53006

Middle Eastern (MID)

AF:

0.159

AC:

599

AN:

3774

European-Non Finnish (NFE)

AF:

0.157

AC:

142353

AN:

906310

Other (OTH)

AF:

0.175

AC:

9191

AN:

52628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

8825

17650

26474

35299

44124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4732

9464

14196

18928

23660

<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:

0.172

AC:

26197

AN:

152110

Hom.:

2810

Cov.:

AF XY:

0.177

AC XY:

13167

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.107

AC:

4433

AN:

41504

American (AMR)

AF:

0.308

AC:

4699

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

550

AN:

3464

East Asian (EAS)

AF:

0.428

AC:

2206

AN:

5152

South Asian (SAS)

AF:

0.113

AC:

544

AN:

4818

European-Finnish (FIN)

AF:

0.234

AC:

2476

AN:

10598

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.159

AC:

10819

AN:

67982

Other (OTH)

AF:

0.173

AC:

365

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1053

2106

3159

4212

5265

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

274

548

822

1096

1370

<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.:

3407

Bravo

AF:

0.178

Asia WGS

AF:

0.234

AC:

816

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.5

(source)

DANN

Benign

0.43

PhyloP100

-0.13

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over