dbSNP rs2255403: PARP1:c.717+87T>C (chr1-226388569-A-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.717+87T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 933,016 control chromosomes in the GnomAD database, including 21,663 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 0.19 ( 3240 hom., cov: 33)

Exomes 𝑓: 0.20 ( 18423 hom. )

Consequence

PARP1
NM_001618.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.30

Publications

12 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:

ENSG00000295046 (HGNC:):

ENSG00000295046 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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP1	NM_001618.4 link	c.717+87T>C		intron_variant	Intron 5 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.717+87T>C		intron_variant	Intron 5 of 22	1	NM_001618.4	ENSP00000355759.5		P09874

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28835

AN:

152128

Hom.:

3228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.185

GnomAD4 exome

AF:

0.198

AC:

154880

AN:

780770

Hom.:

18423

AF XY:

0.194

AC XY:

80613

AN XY:

415112

show subpopulations

African (AFR)

AF:

0.155

AC:

3177

AN:

20442

American (AMR)

AF:

0.407

AC:

17430

AN:

42816

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

3574

AN:

21668

East Asian (EAS)

AF:

0.466

AC:

17000

AN:

36446

South Asian (SAS)

AF:

0.184

AC:

13203

AN:

71776

European-Finnish (FIN)

AF:

0.234

AC:

12298

AN:

52660

Middle Eastern (MID)

AF:

0.164

AC:

729

AN:

4456

European-Non Finnish (NFE)

AF:

0.163

AC:

80172

AN:

492670

Other (OTH)

AF:

0.193

AC:

7297

AN:

37836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

6339

12678

19017

25356

31695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1740

3480

5220

6960

8700

<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:

0.190

AC:

28899

AN:

152246

Hom.:

3240

Cov.:

AF XY:

0.196

AC XY:

14572

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.153

AC:

6370

AN:

41566

American (AMR)

AF:

0.311

AC:

4755

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

579

AN:

3468

East Asian (EAS)

AF:

0.468

AC:

2422

AN:

5178

South Asian (SAS)

AF:

0.197

AC:

951

AN:

4824

European-Finnish (FIN)

AF:

0.232

AC:

2463

AN:

10596

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.160

AC:

10858

AN:

68008

Other (OTH)

AF:

0.187

AC:

396

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1164

2327

3491

4654

5818

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

306

612

918

1224

1530

<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:

0.170

Hom.:

353

Bravo

AF:

0.196

Asia WGS

AF:

0.298

AC:

1035

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.4

(source)

DANN

Benign

0.43

PhyloP100

2.3

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