Variant 1-17342068-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_012387.3(PADI4):c.778G>A(p.Asp260Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,613,568 control chromosomes in the GnomAD database, including 13,423 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 0.096 ( 962 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12461 hom. )

Consequence

PADI4
NM_012387.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.621

Variant links:

Genes affected

PADI4 (HGNC:18368): (peptidyl arginine deiminase 4) This gene is a member of a gene family which encodes enzymes responsible for the conversion of arginine residues to citrulline residues. This gene may play a role in granulocyte and macrophage development leading to inflammation and immune response. [provided by RefSeq, Jul 2008]

PADI4 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=0.002902478).

BP6

Variant 1-17342068-G-A is Benign according to our data. Variant chr1-17342068-G-A is described in ClinVar as [Benign]. Clinvar id is 3056879.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI4	NM_012387.3 linkuse as main transcript	c.778G>A	p.Asp260Asn	missense_variant	7/16	ENST00000375448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI4	ENST00000375448.4 linkuse as main transcript	c.778G>A	p.Asp260Asn	missense_variant	7/16	1	NM_012387.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0964

AC:

14667

AN:

152072

Hom.:

963

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0298

Gnomad AMI

AF:

0.317

Gnomad AMR

AF:

0.0790

Gnomad ASJ

AF:

0.0867

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.0446

Gnomad FIN

AF:

0.167

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.0955

GnomAD3 exomes

AF:

0.101

AC:

25341

AN:

251420

Hom.:

1708

AF XY:

0.103

AC XY:

13952

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.0272

Gnomad AMR exome

AF:

0.0501

Gnomad ASJ exome

AF:

0.0843

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0455

Gnomad FIN exome

AF:

0.167

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.123

AC:

179573

AN:

1461378

Hom.:

12461

Cov.:

AF XY:

0.122

AC XY:

88451

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.0252

Gnomad4 AMR exome

AF:

0.0523

Gnomad4 ASJ exome

AF:

0.0852

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0474

Gnomad4 FIN exome

AF:

0.167

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.0963

AC:

14662

AN:

152190

Hom.:

962

Cov.:

AF XY:

0.0960

AC XY:

7144

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0297

Gnomad4 AMR

AF:

0.0789

Gnomad4 ASJ

AF:

0.0867

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.0445

Gnomad4 FIN

AF:

0.167

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.0945

Alfa

AF:

0.121

Hom.:

2054

Bravo

AF:

0.0848

TwinsUK

AF:

0.134

AC:

496

ALSPAC

AF:

0.139

AC:

535

ESP6500AA

AF:

0.0297

AC:

131

ESP6500EA

AF:

0.129

AC:

1107

ExAC

AF:

0.103

AC:

12476

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.132

EpiControl

AF:

0.136

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PADI4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 09, 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

0.066

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.1

DANN

Benign

0.89

DEOGEN2

Benign

0.042

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.010

MetaRNN

Benign

0.0029

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.75

REVEL

Benign

0.018

Sift

Benign

0.35

Sift4G

Benign

0.17

Polyphen

0.011

Vest4

0.014

MPC

0.11

ClinPred

0.00080

GERP RS

1.3

Varity_R

0.092

gMVP

0.20

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