Genetic Variant PADI4:c.408+83C>T (chr1-17336309-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012387.3(PADI4):c.408+83C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 919,052 control chromosomes in the GnomAD database, including 183,640 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.63 ( 30470 hom., cov: 33)

Exomes 𝑓: 0.63 ( 153170 hom. )

Consequence

PADI4
NM_012387.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.40

Publications

12 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012387.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	NM_012387.3	MANE Select	c.408+83C>T		intron	N/A	NP_036519.2	Q9UM07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	ENST00000375448.4	TSL:1 MANE Select	c.408+83C>T		intron	N/A	ENSP00000364597.4	Q9UM07

Frequencies

GnomAD3 genomes

AF:

0.632

AC:

96053

AN:

152006

Hom.:

30456

Cov.:

show subpopulations

Gnomad AFR

AF:

0.617

Gnomad AMI

AF:

0.690

Gnomad AMR

AF:

0.593

Gnomad ASJ

AF:

0.651

Gnomad EAS

AF:

0.641

Gnomad SAS

AF:

0.584

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.617

Gnomad NFE

AF:

0.649

Gnomad OTH

AF:

0.600

GnomAD4 exome

AF:

0.630

AC:

483050

AN:

766928

Hom.:

153170

AF XY:

0.629

AC XY:

255341

AN XY:

405856

show subpopulations

African (AFR)

AF:

0.611

AC:

12399

AN:

20282

American (AMR)

AF:

0.539

AC:

21682

AN:

40228

Ashkenazi Jewish (ASJ)

AF:

0.639

AC:

13628

AN:

21336

East Asian (EAS)

AF:

0.642

AC:

23248

AN:

36204

South Asian (SAS)

AF:

0.572

AC:

40627

AN:

70966

European-Finnish (FIN)

AF:

0.644

AC:

33585

AN:

52154

Middle Eastern (MID)

AF:

0.592

AC:

2625

AN:

4434

European-Non Finnish (NFE)

AF:

0.645

AC:

311783

AN:

483726

Other (OTH)

AF:

0.624

AC:

23473

AN:

37598

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

8649

17297

25946

34594

43243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4430

8860

13290

17720

22150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.632

AC:

96109

AN:

152124

Hom.:

30470

Cov.:

AF XY:

0.633

AC XY:

47044

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.617

AC:

25610

AN:

41500

American (AMR)

AF:

0.593

AC:

9056

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.651

AC:

2260

AN:

3472

East Asian (EAS)

AF:

0.641

AC:

3315

AN:

5174

South Asian (SAS)

AF:

0.582

AC:

2808

AN:

4822

European-Finnish (FIN)

AF:

0.652

AC:

6899

AN:

10578

Middle Eastern (MID)

AF:

0.633

AC:

186

AN:

294

European-Non Finnish (NFE)

AF:

0.649

AC:

44097

AN:

67980

Other (OTH)

AF:

0.592

AC:

1250

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1871

3742

5614

7485

9356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

790

1580

2370

3160

3950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.640

Hom.:

4066

Bravo

AF:

0.624

Asia WGS

AF:

0.569

AC:

1978

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.018

(source)

DANN

Benign

0.84

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over