Variant chr1-17331121-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_012387.3(PADI4):c.245T>C(p.Val82Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 1,610,008 control chromosomes in the GnomAD database, including 268,305 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,association (no stars).

Frequency

Genomes: 𝑓 0.56 ( 23863 hom., cov: 33)

Exomes 𝑓: 0.58 ( 244442 hom. )

Consequence

PADI4
NM_012387.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.25

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=5.8372883E-5).

BP6

Variant 1-17331121-T-C is Benign according to our data. Variant chr1-17331121-T-C is described in ClinVar as [Benign, association]. Clinvar id is 972893.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 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.245T>C	p.Val82Ala	missense_variant	2/16	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4 linkuse as main transcript	c.245T>C	p.Val82Ala	missense_variant	2/16	1	NM_012387.3	ENSP00000364597	P1
PADI4	ENST00000375453.5 linkuse as main transcript	c.245T>C	p.Val82Ala	missense_variant	2/4	2		ENSP00000364602

Frequencies

GnomAD3 genomes

AF:

0.558

AC:

84813

AN:

151922

Hom.:

23868

Cov.:

show subpopulations

Gnomad AFR

AF:

0.502

Gnomad AMI

AF:

0.644

Gnomad AMR

AF:

0.551

Gnomad ASJ

AF:

0.618

Gnomad EAS

AF:

0.591

Gnomad SAS

AF:

0.538

Gnomad FIN

AF:

0.593

Gnomad MID

AF:

0.581

Gnomad NFE

AF:

0.584

Gnomad OTH

AF:

0.537

GnomAD3 exomes

AF:

0.562

AC:

139062

AN:

247580

Hom.:

39496

AF XY:

0.565

AC XY:

75670

AN XY:

133914

show subpopulations

Gnomad AFR exome

AF:

0.498

Gnomad AMR exome

AF:

0.502

Gnomad ASJ exome

AF:

0.596

Gnomad EAS exome

AF:

0.578

Gnomad SAS exome

AF:

0.527

Gnomad FIN exome

AF:

0.590

Gnomad NFE exome

AF:

0.586

Gnomad OTH exome

AF:

0.574

GnomAD4 exome

AF:

0.578

AC:

842352

AN:

1457968

Hom.:

244442

Cov.:

AF XY:

0.577

AC XY:

418665

AN XY:

725250

show subpopulations

Gnomad4 AFR exome

AF:

0.498

Gnomad4 AMR exome

AF:

0.514

Gnomad4 ASJ exome

AF:

0.604

Gnomad4 EAS exome

AF:

0.593

Gnomad4 SAS exome

AF:

0.533

Gnomad4 FIN exome

AF:

0.587

Gnomad4 NFE exome

AF:

0.586

Gnomad4 OTH exome

AF:

0.561

GnomAD4 genome

AF:

0.558

AC:

84845

AN:

152040

Hom.:

23863

Cov.:

AF XY:

0.558

AC XY:

41491

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.502

Gnomad4 AMR

AF:

0.551

Gnomad4 ASJ

AF:

0.618

Gnomad4 EAS

AF:

0.591

Gnomad4 SAS

AF:

0.536

Gnomad4 FIN

AF:

0.593

Gnomad4 NFE

AF:

0.584

Gnomad4 OTH

AF:

0.530

Alfa

AF:

0.579

Hom.:

55324

Bravo

AF:

0.552

TwinsUK

AF:

0.587

AC:

2176

ALSPAC

AF:

0.591

AC:

2278

ESP6500AA

AF:

0.509

AC:

2242

ESP6500EA

AF:

0.576

AC:

4957

ExAC

AF:

0.564

AC:

68425

Asia WGS

AF:

0.488

AC:

1698

AN:

3478

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

0.053

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.6

DANN

Benign

0.26

DEOGEN2

Benign

0.0048

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00064

MetaRNN

Benign

0.000058

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.4

.;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

2.3

N;N

REVEL

Benign

0.10

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.018

MPC

0.13

ClinPred

0.0022

GERP RS

4.7

Varity_R

0.052

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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