Genetic Variant NM_001618.4:c.717+61C>T (chr1-226388595-G-A) – 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+61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,184,648 control chromosomes in the GnomAD database, including 22,900 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 0.23 ( 4644 hom., cov: 33)

Exomes 𝑓: 0.18 ( 18256 hom. )

Consequence

PARP1
NM_001618.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.169

Publications

16 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:

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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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP1	NM_001618.4 link	c.717+61C>T		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+61C>T		intron_variant	Intron 5 of 22	1	NM_001618.4	ENSP00000355759.5		P09874

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34263

AN:

152090

Hom.:

4641

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.202

GnomAD4 exome

AF:

0.182

AC:

187714

AN:

1032440

Hom.:

18256

AF XY:

0.181

AC XY:

96589

AN XY:

533452

show subpopulations

African (AFR)

AF:

0.385

AC:

9775

AN:

25414

American (AMR)

AF:

0.128

AC:

5639

AN:

44084

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

3386

AN:

23332

East Asian (EAS)

AF:

0.327

AC:

12368

AN:

37816

South Asian (SAS)

AF:

0.181

AC:

14004

AN:

77330

European-Finnish (FIN)

AF:

0.169

AC:

8953

AN:

53112

Middle Eastern (MID)

AF:

0.174

AC:

862

AN:

4964

European-Non Finnish (NFE)

AF:

0.172

AC:

123944

AN:

720316

Other (OTH)

AF:

0.191

AC:

8783

AN:

46072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

7912

15824

23736

31648

39560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3716

7432

11148

14864

18580

<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:

0.225

AC:

34288

AN:

152208

Hom.:

4644

Cov.:

AF XY:

0.224

AC XY:

16637

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.365

AC:

15155

AN:

41504

American (AMR)

AF:

0.142

AC:

2179

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

480

AN:

3472

East Asian (EAS)

AF:

0.338

AC:

1752

AN:

5190

South Asian (SAS)

AF:

0.176

AC:

850

AN:

4824

European-Finnish (FIN)

AF:

0.166

AC:

1761

AN:

10596

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.169

AC:

11504

AN:

68006

Other (OTH)

AF:

0.200

AC:

423

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1349

2698

4046

5395

6744

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.186

Hom.:

12407

Bravo

AF:

0.233

Asia WGS

AF:

0.244

AC:

847

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.2

(source)

DANN

Benign

0.33

PhyloP100

0.17

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