Variant 1-226367601-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001618.4(PARP1):c.2285T>C(p.Val762Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,613,852 control chromosomes in the GnomAD database, including 27,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2595 hom., cov: 32)

Exomes 𝑓: 0.17 ( 24640 hom. )

Consequence

PARP1
NM_001618.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 8.94

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029218793).

BP6

Variant 1-226367601-A-G is Benign according to our data. Variant chr1-226367601-A-G is described in ClinVar as [Benign]. Clinvar id is 1261945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP1	NM_001618.4 linkuse as main transcript	c.2285T>C	p.Val762Ala	missense_variant	17/23	ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10 linkuse as main transcript	c.2285T>C	p.Val762Ala	missense_variant	17/23	1	NM_001618.4	ENSP00000355759	P1

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23915

AN:

152050

Hom.:

2589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0539

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.302

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.164

GnomAD3 exomes

AF:

0.213

AC:

53567

AN:

251412

Hom.:

7750

AF XY:

0.200

AC XY:

27205

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0487

Gnomad AMR exome

AF:

0.423

Gnomad ASJ exome

AF:

0.160

Gnomad EAS exome

AF:

0.448

Gnomad SAS exome

AF:

0.103

Gnomad FIN exome

AF:

0.234

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.169

AC:

247339

AN:

1461684

Hom.:

24640

Cov.:

AF XY:

0.167

AC XY:

121143

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.0486

Gnomad4 AMR exome

AF:

0.402

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.420

Gnomad4 SAS exome

AF:

0.107

Gnomad4 FIN exome

AF:

0.233

Gnomad4 NFE exome

AF:

0.157

Gnomad4 OTH exome

AF:

0.169

GnomAD4 genome

AF:

0.157

AC:

23938

AN:

152168

Hom.:

2595

Cov.:

AF XY:

0.163

AC XY:

12120

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0539

Gnomad4 AMR

AF:

0.303

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.429

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.234

Gnomad4 NFE

AF:

0.159

Gnomad4 OTH

AF:

0.166

Alfa

AF:

0.165

Hom.:

6011

Bravo

AF:

0.162

TwinsUK

AF:

0.147

AC:

544

ALSPAC

AF:

0.159

AC:

612

ESP6500AA

AF:

0.0529

AC:

233

ESP6500EA

AF:

0.159

AC:

1371

ExAC

AF:

0.202

AC:

24493

Asia WGS

AF:

0.229

AC:

798

AN:

3478

EpiCase

AF:

0.149

EpiControl

AF:

0.155

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 08, 2019	This variant is associated with the following publications: (PMID: 24392019, 29484706, 23633189, 15342424, 23040216, 24853559, 24489833, 22624032, 23608917, 23073772, 18716896, 23910651, 19484672, 18054108, 21037106, 20196871, 17214964) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0029

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

5.5e-11

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.3

REVEL

Benign

0.18

Sift

Benign

0.18

Sift4G

Benign

0.51

Polyphen

0.73

Vest4

0.31

MPC

0.84

ClinPred

0.055

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.58

gMVP

0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over