Variant 1-226363128-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 -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 id 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/exons	MANE	UniProt
PARP1	NM_001618.4 linkuse as main transcript	c.2819A>G	p.Lys940Arg	missense_variant	21/23	ENST00000366794.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP1	ENST00000366794.10 linkuse as main transcript	c.2819A>G	p.Lys940Arg	missense_variant	21/23	1	NM_001618.4	P1

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

GnomAD3 exomes

AF:

0.0124

AC:

3116

AN:

251478

Hom.:

126

AF XY:

0.0158

AC XY:

2154

AN XY:

135908

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 SAS exome

AF:

0.0771

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

Gnomad4 AFR exome

AF:

0.00290

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.00861

Gnomad4 EAS exome

AF:

0.0453

Gnomad4 SAS exome

AF:

0.0760

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000415

Gnomad4 OTH exome

AF:

0.00833

GnomAD4 genome

AF:

0.00508

AC:

773

AN:

152308

Hom.:

Cov.:

AF XY:

0.00666

AC XY:

496

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00226

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.0381

Gnomad4 SAS

AF:

0.0839

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00160

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 16, 2019

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

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

MutationTaster

Benign

1.0

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

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

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