Variant rs1805404 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001618.4(PARP1):c.243C>T(p.Asp81Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,614,006 control chromosomes in the GnomAD database, including 27,930 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 0.18 ( 2956 hom., cov: 33)

Exomes 𝑓: 0.17 ( 24974 hom. )

Consequence

PARP1
NM_001618.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.16

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:

PARP1 (HGNC:):

PARP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP7

Synonymous conserved (PhyloP=3.16 with no splicing effect.

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.243C>T	p.Asp81Asp	synonymous_variant	2/23	ENST00000366794.10	NP_001609.2	P09874A0A024R3T8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10 linkuse as main transcript	c.243C>T	p.Asp81Asp	synonymous_variant	2/23	1	NM_001618.4	ENSP00000355759.5		P09874

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27223

AN:

152084

Hom.:

2944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.233

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.177

GnomAD3 exomes

AF:

0.218

AC:

54895

AN:

251372

Hom.:

7918

AF XY:

0.204

AC XY:

27728

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.426

Gnomad ASJ exome

AF:

0.159

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:

0.194

GnomAD4 exome

AF:

0.171

AC:

250468

AN:

1461804

Hom.:

24974

Cov.:

AF XY:

0.168

AC XY:

122451

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.128

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.421

Gnomad4 SAS exome

AF:

0.107

Gnomad4 FIN exome

AF:

0.233

Gnomad4 NFE exome

AF:

0.157

Gnomad4 OTH exome

AF:

0.175

GnomAD4 genome

AF:

0.179

AC:

27278

AN:

152202

Hom.:

2956

Cov.:

AF XY:

0.184

AC XY:

13676

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.131

Gnomad4 AMR

AF:

0.310

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.429

Gnomad4 SAS

AF:

0.113

Gnomad4 FIN

AF:

0.233

Gnomad4 NFE

AF:

0.159

Gnomad4 OTH

AF:

0.178

Alfa

AF:

0.145

Hom.:

975

Bravo

AF:

0.186

Asia WGS

AF:

0.242

AC:

842

AN:

3478

EpiCase

AF:

0.149

EpiControl

AF:

0.155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.49

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over