Genetic Variant PADI4:c.1048-34C>T (chr1-17347907-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.1048-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 1,281,122 control chromosomes in the GnomAD database, including 116,933 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 0.45 ( 15916 hom., cov: 32)

Exomes 𝑓: 0.42 ( 101017 hom. )

Consequence

PADI4
NM_012387.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.34

Publications

35 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:

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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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	NM_012387.3	MANE Select	c.1048-34C>T		intron	N/A	NP_036519.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PADI4	ENST00000375448.4	TSL:1 MANE Select	c.1048-34C>T	intron	N/A	ENSP00000364597.4
PADI4	ENST00000468945.1	TSL:2	n.107-34C>T	intron	N/A
PADI4	ENST00000487048.5	TSL:3	n.-20C>T	upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.453

AC:

68846

AN:

151888

Hom.:

15905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.497

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.475

Gnomad ASJ

AF:

0.471

Gnomad EAS

AF:

0.640

Gnomad SAS

AF:

0.483

Gnomad FIN

AF:

0.404

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.446

GnomAD2 exomes

AF:

0.428

AC:

79169

AN:

184870

AF XY:

0.428

show subpopulations

Gnomad AFR exome

AF:

0.493

Gnomad AMR exome

AF:

0.411

Gnomad ASJ exome

AF:

0.421

Gnomad EAS exome

AF:

0.607

Gnomad FIN exome

AF:

0.398

Gnomad NFE exome

AF:

0.402

Gnomad OTH exome

AF:

0.411

GnomAD4 exome

AF:

0.418

AC:

472273

AN:

1129116

Hom.:

101017

Cov.:

AF XY:

0.419

AC XY:

235008

AN XY:

560842

show subpopulations

African (AFR)

AF:

0.488

AC:

12797

AN:

26224

American (AMR)

AF:

0.424

AC:

13904

AN:

32774

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

8361

AN:

18698

East Asian (EAS)

AF:

0.624

AC:

21720

AN:

34800

South Asian (SAS)

AF:

0.435

AC:

26229

AN:

60246

European-Finnish (FIN)

AF:

0.393

AC:

18998

AN:

48284

Middle Eastern (MID)

AF:

0.460

AC:

2204

AN:

4790

European-Non Finnish (NFE)

AF:

0.406

AC:

347630

AN:

855922

Other (OTH)

AF:

0.431

AC:

20430

AN:

47378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

12612

25225

37837

50450

63062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10928

21856

32784

43712

54640

<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:

0.453

AC:

68898

AN:

152006

Hom.:

15916

Cov.:

AF XY:

0.455

AC XY:

33831

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.497

AC:

20606

AN:

41458

American (AMR)

AF:

0.474

AC:

7254

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.471

AC:

1635

AN:

3470

East Asian (EAS)

AF:

0.640

AC:

3286

AN:

5136

South Asian (SAS)

AF:

0.482

AC:

2323

AN:

4818

European-Finnish (FIN)

AF:

0.404

AC:

4263

AN:

10558

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.416

AC:

28242

AN:

67964

Other (OTH)

AF:

0.441

AC:

930

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1919

3838

5757

7676

9595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.424

Hom.:

3733

Bravo

AF:

0.462

Asia WGS

AF:

0.515

AC:

1788

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.59

(source)

DANN

Benign

0.64

PhyloP100

-4.3

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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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