dbSNP rs8679: PARP1:c.*607T>C (chr1-226360853-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.*607T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 227,816 control chromosomes in the GnomAD database, including 4,488 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 ( 2638 hom., cov: 31)

Exomes 𝑓: 0.21 ( 1850 hom. )

Consequence

PARP1
NM_001618.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.511

Publications

53 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=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP1	NM_001618.4 link	c.*607T>C		3_prime_UTR_variant	Exon 23 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.*607T>C		3_prime_UTR_variant	Exon 23 of 23	1	NM_001618.4	ENSP00000355759.5		P09874

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25230

AN:

152106

Hom.:

2639

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0610

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.0595

Gnomad SAS

AF:

0.248

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.197

GnomAD4 exome

AF:

0.206

AC:

15609

AN:

75592

Hom.:

1850

Cov.:

AF XY:

0.211

AC XY:

7347

AN XY:

34902

show subpopulations

African (AFR)

AF:

0.0567

AC:

203

AN:

3582

American (AMR)

AF:

0.162

AC:

387

AN:

2396

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

1374

AN:

4740

East Asian (EAS)

AF:

0.0648

AC:

692

AN:

10674

South Asian (SAS)

AF:

0.269

AC:

191

AN:

710

European-Finnish (FIN)

AF:

0.104

AC:

AN:

Middle Eastern (MID)

AF:

0.284

AC:

131

AN:

462

European-Non Finnish (NFE)

AF:

0.242

AC:

11304

AN:

46726

Other (OTH)

AF:

0.211

AC:

1322

AN:

6254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

562

1124

1686

2248

2810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.166

AC:

25223

AN:

152224

Hom.:

2638

Cov.:

AF XY:

0.161

AC XY:

11968

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0608

AC:

2527

AN:

41550

American (AMR)

AF:

0.179

AC:

2741

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

1029

AN:

3466

East Asian (EAS)

AF:

0.0596

AC:

309

AN:

5184

South Asian (SAS)

AF:

0.248

AC:

1192

AN:

4814

European-Finnish (FIN)

AF:

0.118

AC:

1252

AN:

10598

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.228

AC:

15499

AN:

67992

Other (OTH)

AF:

0.195

AC:

411

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1035

2070

3105

4140

5175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.210

Hom.:

5406

Bravo

AF:

0.165

Asia WGS

AF:

0.145

AC:

506

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.80

(source)

DANN

Benign

0.63

PhyloP100

-0.51

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