Variant 1-226383047-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001618.4(PARP1):c.1148C>A(p.Ser383Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00228 in 1,612,654 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 8 hom. )

Consequence

PARP1
NM_001618.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.87

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012862891).

BP6

Variant 1-226383047-G-T is Benign according to our data. Variant chr1-226383047-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3039691.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 247 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP1	NM_001618.4 linkuse as main transcript	c.1148C>A	p.Ser383Tyr	missense_variant	8/23	ENST00000366794.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP1	ENST00000366794.10 linkuse as main transcript	c.1148C>A	p.Ser383Tyr	missense_variant	8/23	1	NM_001618.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

247

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00300

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00143

AC:

360

AN:

251400

Hom.:

AF XY:

0.00147

AC XY:

200

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000947

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00266

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00234

AC:

3423

AN:

1460318

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

1729

AN XY:

726440

show subpopulations

Gnomad4 AFR exome

AF:

0.000479

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000824

Gnomad4 FIN exome

AF:

0.000599

Gnomad4 NFE exome

AF:

0.00287

Gnomad4 OTH exome

AF:

0.00164

GnomAD4 genome

AF:

0.00162

AC:

247

AN:

152336

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000470

Gnomad4 NFE

AF:

0.00300

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00263

Hom.:

Bravo

AF:

0.00160

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00141

AC:

171

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00229

EpiControl

AF:

0.00255

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PARP1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 03, 2020

This variant is classified as likely 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

0.12

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.47

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.16

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.71

M_CAP

Benign

0.014

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.79

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.7

REVEL

Benign

0.11

Sift

Uncertain

0.029

Sift4G

Uncertain

0.042

Polyphen

0.73

Vest4

0.45

MVP

0.70

MPC

0.63

ClinPred

0.031

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.068

gMVP

0.31

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