dbSNP rs3219145: PARP1:p.Lys940Arg (chr1-226363128-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001618.4(PARP1):c.2819A>G(p.Lys940Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00648 in 1,613,868 control chromosomes in the GnomAD database, including 432 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0051 ( 27 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 405 hom. )

Consequence

PARP1
NM_001618.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.99

Publications

38 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030174851).

BP6

Variant 1-226363128-T-C is Benign according to our data. Variant chr1-226363128-T-C is described in ClinVar as Benign. ClinVar VariationId is 3041509.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP1	NM_001618.4 link	c.2819A>G	p.Lys940Arg	missense_variant	Exon 21 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.2819A>G	p.Lys940Arg	missense_variant	Exon 21 of 23	1	NM_001618.4	ENSP00000355759.5		P09874

Frequencies

GnomAD3 genomes

AF:

0.00506

AC:

770

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.0378

Gnomad SAS

AF:

0.0840

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.0124

AC:

3116

AN:

251478

AF XY:

0.0158

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00923

Gnomad EAS exome

AF:

0.0285

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000457

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00663

AC:

9690

AN:

1461560

Hom.:

405

Cov.:

AF XY:

0.00870

AC XY:

6325

AN XY:

727114

show subpopulations

African (AFR)

AF:

0.00290

AC:

AN:

33478

American (AMR)

AF:

0.000604

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00861

AC:

225

AN:

26128

East Asian (EAS)

AF:

0.0453

AC:

1798

AN:

39700

South Asian (SAS)

AF:

0.0760

AC:

6551

AN:

86210

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00451

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000415

AC:

461

AN:

1111754

Other (OTH)

AF:

0.00833

AC:

503

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

590

1180

1770

2360

2950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<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:

0.00508

AC:

773

AN:

152308

Hom.:

Cov.:

AF XY:

0.00666

AC XY:

496

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

41558

American (AMR)

AF:

0.000588

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00922

AC:

AN:

3472

East Asian (EAS)

AF:

0.0381

AC:

197

AN:

5176

South Asian (SAS)

AF:

0.0839

AC:

405

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000367

AC:

AN:

68036

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

107

143

179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00235

Hom.:

Bravo

AF:

0.00311

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.0135

AC:

1634

Asia WGS

AF:

0.0550

AC:

192

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PARP1-related disorder

Benign:1

Nov 16, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0030

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.7

PhyloP100

8.0

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.23

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.013

Polyphen

0.88

Vest4

0.18

MPC

0.22

ClinPred

0.028

GERP RS

5.8

Varity_R

0.86

gMVP

0.55

Mutation Taster

=79/21

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over