Genetic Variant PADI4:c.1155+309T>C (chr1-17348357-T-C) – 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.1155+309T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 223,308 control chromosomes in the GnomAD database, including 44,632 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 ( 31353 hom., cov: 33)

Exomes 𝑓: 0.59 ( 13279 hom. )

Consequence

PADI4
NM_012387.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.962

Publications

7 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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 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.1155+309T>C		intron	N/A	NP_036519.2	Q9UM07

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PADI4	ENST00000375448.4	TSL:1 MANE Select	c.1155+309T>C	intron	N/A	ENSP00000364597.4	Q9UM07
PADI4	ENST00000487048.5	TSL:3	n.122+309T>C	intron	N/A
PADI4	ENST00000468945.1	TSL:2	n.*150T>C	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.641

AC:

97345

AN:

151856

Hom.:

31342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.598

Gnomad AMI

AF:

0.718

Gnomad AMR

AF:

0.608

Gnomad ASJ

AF:

0.674

Gnomad EAS

AF:

0.643

Gnomad SAS

AF:

0.596

Gnomad FIN

AF:

0.667

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.672

Gnomad OTH

AF:

0.618

GnomAD4 exome

AF:

0.593

AC:

42276

AN:

71334

Hom.:

13279

AF XY:

0.590

AC XY:

21769

AN XY:

36890

show subpopulations

African (AFR)

AF:

0.528

AC:

1586

AN:

3002

American (AMR)

AF:

0.494

AC:

1453

AN:

2942

Ashkenazi Jewish (ASJ)

AF:

0.611

AC:

1627

AN:

2662

East Asian (EAS)

AF:

0.524

AC:

2227

AN:

4252

South Asian (SAS)

AF:

0.446

AC:

1725

AN:

3870

European-Finnish (FIN)

AF:

0.606

AC:

2358

AN:

3890

Middle Eastern (MID)

AF:

0.563

AC:

187

AN:

332

European-Non Finnish (NFE)

AF:

0.620

AC:

28391

AN:

45820

Other (OTH)

AF:

0.596

AC:

2722

AN:

4564

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

782

1564

2346

3128

3910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

280

420

560

700

<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:

0.641

AC:

97404

AN:

151974

Hom.:

31353

Cov.:

AF XY:

0.640

AC XY:

47536

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.599

AC:

24796

AN:

41414

American (AMR)

AF:

0.607

AC:

9263

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.674

AC:

2339

AN:

3470

East Asian (EAS)

AF:

0.643

AC:

3319

AN:

5160

South Asian (SAS)

AF:

0.594

AC:

2865

AN:

4822

European-Finnish (FIN)

AF:

0.667

AC:

7039

AN:

10552

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.671

AC:

45644

AN:

67974

Other (OTH)

AF:

0.611

AC:

1292

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1809

3618

5427

7236

9045

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

792

1584

2376

3168

3960

<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:

0.663

Hom.:

6817

Bravo

AF:

0.634

Asia WGS

AF:

0.582

AC:

2022

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.24

(source)

DANN

Benign

0.31

PhyloP100

-0.96

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