Genetic Variant NM_012387.3:c.408+30C>G (chr1-17336256-C-G) – 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+30C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,587,572 control chromosomes in the GnomAD database, including 349,626 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 0.64 ( 31665 hom., cov: 33)

Exomes 𝑓: 0.66 ( 317961 hom. )

Consequence

PADI4
NM_012387.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0920

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:

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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=-0.98).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 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+30C>G		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+30C>G		intron	N/A	ENSP00000364597.4	Q9UM07

Frequencies

GnomAD3 genomes

AF:

0.643

AC:

97787

AN:

152028

Hom.:

31656

Cov.:

show subpopulations

Gnomad AFR

AF:

0.601

Gnomad AMI

AF:

0.702

Gnomad AMR

AF:

0.601

Gnomad ASJ

AF:

0.671

Gnomad EAS

AF:

0.642

Gnomad SAS

AF:

0.586

Gnomad FIN

AF:

0.686

Gnomad MID

AF:

0.617

Gnomad NFE

AF:

0.675

Gnomad OTH

AF:

0.607

GnomAD2 exomes

AF:

0.634

AC:

157977

AN:

249002

AF XY:

0.637

show subpopulations

Gnomad AFR exome

AF:

0.601

Gnomad AMR exome

AF:

0.534

Gnomad ASJ exome

AF:

0.654

Gnomad EAS exome

AF:

0.628

Gnomad FIN exome

AF:

0.680

Gnomad NFE exome

AF:

0.677

Gnomad OTH exome

AF:

0.638

GnomAD4 exome

AF:

0.664

AC:

952515

AN:

1435426

Hom.:

317961

Cov.:

AF XY:

0.662

AC XY:

473576

AN XY:

715640

show subpopulations

African (AFR)

AF:

0.597

AC:

19686

AN:

32962

American (AMR)

AF:

0.546

AC:

24272

AN:

44436

Ashkenazi Jewish (ASJ)

AF:

0.662

AC:

17185

AN:

25968

East Asian (EAS)

AF:

0.642

AC:

25410

AN:

39560

South Asian (SAS)

AF:

0.578

AC:

49528

AN:

85662

European-Finnish (FIN)

AF:

0.677

AC:

36126

AN:

53350

Middle Eastern (MID)

AF:

0.598

AC:

3426

AN:

5726

European-Non Finnish (NFE)

AF:

0.679

AC:

738520

AN:

1088226

Other (OTH)

AF:

0.644

AC:

38362

AN:

59536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

14975

29950

44926

59901

74876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18792

37584

56376

75168

93960

<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:

0.643

AC:

97835

AN:

152146

Hom.:

31665

Cov.:

AF XY:

0.643

AC XY:

47819

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.602

AC:

24957

AN:

41486

American (AMR)

AF:

0.600

AC:

9177

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.671

AC:

2330

AN:

3472

East Asian (EAS)

AF:

0.642

AC:

3324

AN:

5176

South Asian (SAS)

AF:

0.585

AC:

2820

AN:

4824

European-Finnish (FIN)

AF:

0.686

AC:

7255

AN:

10580

Middle Eastern (MID)

AF:

0.633

AC:

186

AN:

294

European-Non Finnish (NFE)

AF:

0.675

AC:

45879

AN:

68000

Other (OTH)

AF:

0.599

AC:

1267

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1860

3721

5581

7442

9302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

800

1600

2400

3200

4000

<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:

0.659

Hom.:

6098

Bravo

AF:

0.633

Asia WGS

AF:

0.569

AC:

1977

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

2.1

(source)

DANN

Benign

0.38

PhyloP100

-0.092

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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