Variant 1-17334004-G-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_012387.3(PADI4):c.335G>C(p.Gly112Ala) variant causes a missense change. The variant allele was found at a frequency of 0.554 in 1,602,266 control chromosomes in the GnomAD database, including 247,750 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,association (no stars).

Frequency

Genomes: 𝑓 0.54 ( 21992 hom., cov: 31)

Exomes 𝑓: 0.56 ( 225758 hom. )

Consequence

PADI4
NM_012387.3 missense

Scores

Clinical Significance

Benign; association no assertion criteria provided B:1O:1

Conservation

PhyloP100: 3.69

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=9.706947E-5).

BP6

Variant 1-17334004-G-C is Benign according to our data. Variant chr1-17334004-G-C is described in ClinVar as [Benign, association]. Clinvar id is 972895.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI4	NM_012387.3 linkuse as main transcript	c.335G>C	p.Gly112Ala	missense_variant	3/16	ENST00000375448.4	NP_036519.2	Q9UM07

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4 linkuse as main transcript	c.335G>C	p.Gly112Ala	missense_variant	3/16	1	NM_012387.3	ENSP00000364597.4		Q9UM07
PADI4	ENST00000375453.5 linkuse as main transcript	c.335G>C	p.Gly112Ala	missense_variant	3/4	2		ENSP00000364602.1		B1AQ67

Frequencies

GnomAD3 genomes

AF:

0.536

AC:

81347

AN:

151744

Hom.:

22001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.479

Gnomad AMI

AF:

0.635

Gnomad AMR

AF:

0.539

Gnomad ASJ

AF:

0.599

Gnomad EAS

AF:

0.590

Gnomad SAS

AF:

0.535

Gnomad FIN

AF:

0.560

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.521

GnomAD3 exomes

AF:

0.545

AC:

136995

AN:

251246

Hom.:

37763

AF XY:

0.549

AC XY:

74563

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.479

Gnomad AMR exome

AF:

0.497

Gnomad ASJ exome

AF:

0.576

Gnomad EAS exome

AF:

0.578

Gnomad SAS exome

AF:

0.525

Gnomad FIN exome

AF:

0.558

Gnomad NFE exome

AF:

0.564

Gnomad OTH exome

AF:

0.558

GnomAD4 exome

AF:

0.556

AC:

806606

AN:

1450404

Hom.:

225758

Cov.:

AF XY:

0.556

AC XY:

401926

AN XY:

722384

show subpopulations

Gnomad4 AFR exome

AF:

0.476

Gnomad4 AMR exome

AF:

0.507

Gnomad4 ASJ exome

AF:

0.582

Gnomad4 EAS exome

AF:

0.592

Gnomad4 SAS exome

AF:

0.530

Gnomad4 FIN exome

AF:

0.555

Gnomad4 NFE exome

AF:

0.562

Gnomad4 OTH exome

AF:

0.541

GnomAD4 genome

AF:

0.536

AC:

81371

AN:

151862

Hom.:

21992

Cov.:

AF XY:

0.538

AC XY:

39897

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.479

Gnomad4 AMR

AF:

0.539

Gnomad4 ASJ

AF:

0.599

Gnomad4 EAS

AF:

0.590

Gnomad4 SAS

AF:

0.533

Gnomad4 FIN

AF:

0.560

Gnomad4 NFE

AF:

0.558

Gnomad4 OTH

AF:

0.514

Alfa

AF:

0.544

Hom.:

16057

Bravo

AF:

0.531

TwinsUK

AF:

0.566

AC:

2099

ALSPAC

AF:

0.567

AC:

2184

ESP6500AA

AF:

0.486

AC:

2143

ESP6500EA

AF:

0.551

AC:

4738

ExAC

AF:

0.546

AC:

66308

EpiCase

AF:

0.563

EpiControl

AF:

0.561

ClinVar

Significance: Benign; association

Submissions summary: Benign:1Other: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

Oct 17, 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). -

Rheumatoid arthritis;C5441745:Abnormal pulmonary interstitial morphology

Other:1

association, no assertion criteria provided

case-control

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Feb 01, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.037

T;T

Eigen

Benign

0.016

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.79

MetaRNN

Benign

0.000097

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

.;L

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.9

D;N

REVEL

Benign

0.087

Sift

Benign

0.82

T;T

Sift4G

Pathogenic

0.0

D;T

Polyphen

0.64

.;P

Vest4

0.081

MPC

0.14

ClinPred

0.031

GERP RS

4.7

Varity_R

0.42

gMVP

0.29

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