Genetic Variant PARP1:c.-17G>C (chr1-226407946-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.-17G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,610,132 control chromosomes in the GnomAD database, including 28,309 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 0.16 ( 2730 hom., cov: 32)

Exomes 𝑓: 0.17 ( 25579 hom. )

Consequence

PARP1
NM_001618.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.951

Publications

23 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 = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP1	NM_001618.4 link	c.-17G>C		5_prime_UTR_variant	Exon 1 of 23	ENST00000366794.10	NP_001609.2	P09874A0A024R3T8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10 link	c.-17G>C		5_prime_UTR_variant	Exon 1 of 23	1	NM_001618.4	ENSP00000355759.5		P09874

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24523

AN:

151984

Hom.:

2724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0539

Gnomad AMI

AF:

0.0725

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.430

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.137

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.169

GnomAD2 exomes

AF:

0.214

AC:

52583

AN:

246266

AF XY:

0.201

show subpopulations

Gnomad AFR exome

AF:

0.0465

Gnomad AMR exome

AF:

0.418

Gnomad ASJ exome

AF:

0.160

Gnomad EAS exome

AF:

0.443

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.165

Gnomad OTH exome

AF:

0.194

GnomAD4 exome

AF:

0.173

AC:

252465

AN:

1458040

Hom.:

25579

Cov.:

AF XY:

0.170

AC XY:

123645

AN XY:

725378

show subpopulations

African (AFR)

AF:

0.0483

AC:

1612

AN:

33370

American (AMR)

AF:

0.399

AC:

17612

AN:

44186

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

4102

AN:

26008

East Asian (EAS)

AF:

0.420

AC:

16547

AN:

39438

South Asian (SAS)

AF:

0.107

AC:

9221

AN:

86142

European-Finnish (FIN)

AF:

0.263

AC:

13892

AN:

52824

Middle Eastern (MID)

AF:

0.150

AC:

863

AN:

5760

European-Non Finnish (NFE)

AF:

0.160

AC:

178151

AN:

1110118

Other (OTH)

AF:

0.174

AC:

10465

AN:

60194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

10545

21091

31636

42182

52727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6392

12784

19176

25568

31960

<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:

0.161

AC:

24545

AN:

152092

Hom.:

2730

Cov.:

AF XY:

0.168

AC XY:

12516

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0539

AC:

2239

AN:

41550

American (AMR)

AF:

0.305

AC:

4659

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

559

AN:

3470

East Asian (EAS)

AF:

0.430

AC:

2213

AN:

5146

South Asian (SAS)

AF:

0.114

AC:

549

AN:

4824

European-Finnish (FIN)

AF:

0.263

AC:

2781

AN:

10566

Middle Eastern (MID)

AF:

0.130

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.163

AC:

11083

AN:

67928

Other (OTH)

AF:

0.170

AC:

358

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

981

1962

2943

3924

4905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<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:

0.159

Hom.:

387

Bravo

AF:

0.164

Asia WGS

AF:

0.226

AC:

782

AN:

3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

0.95

PromoterAI

-0.024

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

3.2

Mutation Taster

=300/0

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