Genetic Variant PADI4:p.Leu117Leu (chr1-17336167-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_012387.3(PADI4):c.349T>C(p.Leu117Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,607,184 control chromosomes in the GnomAD database, including 353,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign,association (no stars).

Frequency

Genomes: 𝑓 0.64 ( 30890 hom., cov: 32)

Exomes 𝑓: 0.66 ( 322229 hom. )

Consequence

PADI4
NM_012387.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.249

Publications

64 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-17336167-T-C is Benign according to our data. Variant chr1-17336167-T-C is described in ClinVar as [Benign, association]. Clinvar id is 972894.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.249 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3 link	c.349T>C	p.Leu117Leu	synonymous_variant	Exon 4 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.349T>C	p.Leu117Leu	synonymous_variant	Exon 4 of 16	1	NM_012387.3	ENSP00000364597.4		Q9UM07

Frequencies

GnomAD3 genomes

AF:

0.635

AC:

96480

AN:

151842

Hom.:

30885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.574

Gnomad AMI

AF:

0.703

Gnomad AMR

AF:

0.598

Gnomad ASJ

AF:

0.671

Gnomad EAS

AF:

0.641

Gnomad SAS

AF:

0.587

Gnomad FIN

AF:

0.686

Gnomad MID

AF:

0.621

Gnomad NFE

AF:

0.675

Gnomad OTH

AF:

0.601

GnomAD2 exomes

AF:

0.632

AC:

158374

AN:

250564

AF XY:

0.635

show subpopulations

Gnomad AFR exome

AF:

0.572

Gnomad AMR exome

AF:

0.532

Gnomad ASJ exome

AF:

0.655

Gnomad EAS exome

AF:

0.627

Gnomad FIN exome

AF:

0.680

Gnomad NFE exome

AF:

0.676

Gnomad OTH exome

AF:

0.637

GnomAD4 exome

AF:

0.663

AC:

964792

AN:

1455226

Hom.:

322229

Cov.:

AF XY:

0.661

AC XY:

479011

AN XY:

724410

show subpopulations

African (AFR)

AF:

0.570

AC:

19021

AN:

33348

American (AMR)

AF:

0.544

AC:

24308

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.662

AC:

17253

AN:

26068

East Asian (EAS)

AF:

0.642

AC:

25457

AN:

39656

South Asian (SAS)

AF:

0.578

AC:

49780

AN:

86096

European-Finnish (FIN)

AF:

0.677

AC:

36160

AN:

53404

Middle Eastern (MID)

AF:

0.596

AC:

3429

AN:

5754

European-Non Finnish (NFE)

AF:

0.679

AC:

750733

AN:

1106084

Other (OTH)

AF:

0.642

AC:

38651

AN:

60168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

14439

28879

43318

57758

72197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.635

AC:

96521

AN:

151958

Hom.:

30890

Cov.:

AF XY:

0.635

AC XY:

47165

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.574

AC:

23774

AN:

41422

American (AMR)

AF:

0.597

AC:

9115

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.671

AC:

2330

AN:

3472

East Asian (EAS)

AF:

0.641

AC:

3292

AN:

5138

South Asian (SAS)

AF:

0.585

AC:

2822

AN:

4824

European-Finnish (FIN)

AF:

0.686

AC:

7249

AN:

10562

Middle Eastern (MID)

AF:

0.637

AC:

186

AN:

292

European-Non Finnish (NFE)

AF:

0.675

AC:

45857

AN:

67948

Other (OTH)

AF:

0.594

AC:

1256

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1781

3563

5344

7126

8907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.655

Hom.:

97563

Bravo

AF:

0.624

Asia WGS

AF:

0.567

AC:

1971

AN:

3478

EpiCase

AF:

0.665

EpiControl

AF:

0.661

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

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.8

(source)

DANN

Benign

0.65

PhyloP100

0.25

Mutation Taster

=100/0

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

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chr1-17336167-T-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