dbSNP rs2240340: PADI4:c.341-15T>C (chr1-17336144-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_012387.3(PADI4):c.341-15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 1,592,118 control chromosomes in the GnomAD database, including 263,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.54 ( 22893 hom., cov: 32)

Exomes 𝑓: 0.58 ( 240231 hom. )

Consequence

PADI4
NM_012387.3 intron

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: -0.0470

Publications

89 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 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.341-15T>C		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.341-15T>C		intron	N/A	ENSP00000364597.4	Q9UM07

Frequencies

GnomAD3 genomes

AF:

0.545

AC:

82805

AN:

151860

Hom.:

22905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.457

Gnomad AMI

AF:

0.645

Gnomad AMR

AF:

0.546

Gnomad ASJ

AF:

0.618

Gnomad EAS

AF:

0.590

Gnomad SAS

AF:

0.538

Gnomad FIN

AF:

0.593

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.584

Gnomad OTH

AF:

0.528

GnomAD2 exomes

AF:

0.559

AC:

139599

AN:

249740

AF XY:

0.563

show subpopulations

Gnomad AFR exome

AF:

0.454

Gnomad AMR exome

AF:

0.504

Gnomad ASJ exome

AF:

0.596

Gnomad EAS exome

AF:

0.578

Gnomad FIN exome

AF:

0.589

Gnomad NFE exome

AF:

0.586

Gnomad OTH exome

AF:

0.573

GnomAD4 exome

AF:

0.575

AC:

828470

AN:

1440142

Hom.:

240231

Cov.:

AF XY:

0.575

AC XY:

412839

AN XY:

717856

show subpopulations

African (AFR)

AF:

0.452

AC:

14965

AN:

33082

American (AMR)

AF:

0.513

AC:

22863

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.604

AC:

15686

AN:

25984

East Asian (EAS)

AF:

0.593

AC:

23454

AN:

39582

South Asian (SAS)

AF:

0.532

AC:

45687

AN:

85812

European-Finnish (FIN)

AF:

0.587

AC:

31348

AN:

53364

Middle Eastern (MID)

AF:

0.558

AC:

3196

AN:

5724

European-Non Finnish (NFE)

AF:

0.584

AC:

638057

AN:

1092432

Other (OTH)

AF:

0.557

AC:

33214

AN:

59636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

14624

29248

43873

58497

73121

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17376

34752

52128

69504

86880

<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:

0.545

AC:

82823

AN:

151976

Hom.:

22893

Cov.:

AF XY:

0.546

AC XY:

40531

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.457

AC:

18918

AN:

41434

American (AMR)

AF:

0.545

AC:

8324

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.618

AC:

2145

AN:

3472

East Asian (EAS)

AF:

0.590

AC:

3040

AN:

5154

South Asian (SAS)

AF:

0.537

AC:

2591

AN:

4826

European-Finnish (FIN)

AF:

0.593

AC:

6264

AN:

10564

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.584

AC:

39680

AN:

67944

Other (OTH)

AF:

0.521

AC:

1101

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1933

3866

5799

7732

9665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<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:

0.570

Hom.:

35279

Bravo

AF:

0.537

Asia WGS

AF:

0.484

AC:

1683

AN:

3478

ClinVar

ClinVar submissions

Significance:association

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Rheumatoid arthritis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

7.5

(source)

DANN

Benign

0.43

PhyloP100

-0.047

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.42

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.42

Position offset: 0

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