dbSNP rs2301888: PADI4:c.1047+96G>A (chr1-17346235-G-A) – 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.1047+96G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 704,740 control chromosomes in the GnomAD database, including 47,023 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 0.32 ( 8441 hom., cov: 31)

Exomes 𝑓: 0.36 ( 38582 hom. )

Consequence

PADI4
NM_012387.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.38

Publications

42 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

new If you want to explore the variant's impact on the transcript NM_012387.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 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.1047+96G>A		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.1047+96G>A		intron	N/A	ENSP00000364597.4	Q9UM07
	PADI4	ENST00000468945.1	TSL:2	n.106+96G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48116

AN:

151850

Hom.:

8451

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.199

Gnomad AMR

AF:

0.396

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.584

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.333

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.329

GnomAD4 exome

AF:

0.364

AC:

201481

AN:

552772

Hom.:

38582

AF XY:

0.368

AC XY:

108548

AN XY:

294726

show subpopulations

African (AFR)

AF:

0.174

AC:

2539

AN:

14624

American (AMR)

AF:

0.396

AC:

9500

AN:

24008

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

6377

AN:

15756

East Asian (EAS)

AF:

0.578

AC:

18561

AN:

32096

South Asian (SAS)

AF:

0.429

AC:

23372

AN:

54502

European-Finnish (FIN)

AF:

0.327

AC:

15173

AN:

46426

Middle Eastern (MID)

AF:

0.375

AC:

835

AN:

2228

European-Non Finnish (NFE)

AF:

0.343

AC:

114604

AN:

333828

Other (OTH)

AF:

0.359

AC:

10520

AN:

29304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5964

11927

17891

23854

29818

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1132

2264

3396

4528

5660

<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:

0.316

AC:

48096

AN:

151968

Hom.:

8441

Cov.:

AF XY:

0.323

AC XY:

23970

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.178

AC:

7371

AN:

41476

American (AMR)

AF:

0.395

AC:

6040

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.419

AC:

1452

AN:

3468

East Asian (EAS)

AF:

0.584

AC:

2990

AN:

5116

South Asian (SAS)

AF:

0.450

AC:

2170

AN:

4822

European-Finnish (FIN)

AF:

0.333

AC:

3523

AN:

10572

Middle Eastern (MID)

AF:

0.435

AC:

127

AN:

292

European-Non Finnish (NFE)

AF:

0.347

AC:

23558

AN:

67926

Other (OTH)

AF:

0.324

AC:

684

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1573

3146

4720

6293

7866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.356

Hom.:

9128

Bravo

AF:

0.318

Asia WGS

AF:

0.421

AC:

1462

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

6.5

(source)

DANN

Benign

0.47

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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