Genetic Variant PADI4:p.Gly112Ala (chr1-17334004-G-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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

Publications

94 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PADI4	NM_012387.3 link	c.335G>C	p.Gly112Ala	missense_variant	Exon 3 of 16	ENST00000375448.4	NP_036519.2	Q9UM07

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4 link	c.335G>C	p.Gly112Ala	missense_variant	Exon 3 of 16	1	NM_012387.3	ENSP00000364597.4		Q9UM07
PADI4	ENST00000375453.5 link	c.335G>C	p.Gly112Ala	missense_variant	Exon 3 of 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

GnomAD2 exomes

AF:

0.545

AC:

136995

AN:

251246

AF XY:

0.549

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 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

African (AFR)

AF:

0.476

AC:

15818

AN:

33252

American (AMR)

AF:

0.507

AC:

22659

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.582

AC:

15161

AN:

26052

East Asian (EAS)

AF:

0.592

AC:

23470

AN:

39626

South Asian (SAS)

AF:

0.530

AC:

45604

AN:

86042

European-Finnish (FIN)

AF:

0.555

AC:

29594

AN:

53356

Middle Eastern (MID)

AF:

0.559

AC:

3211

AN:

5746

European-Non Finnish (NFE)

AF:

0.562

AC:

618607

AN:

1101616

Other (OTH)

AF:

0.541

AC:

32482

AN:

60024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

15278

30556

45833

61111

76389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.536

AC:

81371

AN:

151862

Hom.:

21992

Cov.:

AF XY:

0.538

AC XY:

39897

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.479

AC:

19842

AN:

41406

American (AMR)

AF:

0.539

AC:

8215

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.599

AC:

2073

AN:

3462

East Asian (EAS)

AF:

0.590

AC:

3024

AN:

5124

South Asian (SAS)

AF:

0.533

AC:

2567

AN:

4812

European-Finnish (FIN)

AF:

0.560

AC:

5911

AN:

10550

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.558

AC:

37909

AN:

67956

Other (OTH)

AF:

0.514

AC:

1081

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1936

3871

5807

7742

9678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Feb 01, 2020

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance:association

Review Status:no assertion criteria provided

Collection Method:case-control

- -

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

(source)

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

PhyloP100

3.7

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

Mutation Taster

=68/32

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr1-17334004-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over