Genetic Variant PADI4:c.93-143C>T (chr1-17330826-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_012387.3(PADI4):c.93-143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 576,050 control chromosomes in the GnomAD database, including 505 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 0.031 ( 96 hom., cov: 33)

Exomes 𝑓: 0.039 ( 409 hom. )

Consequence

PADI4
NM_012387.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.637

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0314 (4777/152294) while in subpopulation NFE AF = 0.0473 (3217/68010). AF 95% confidence interval is 0.0459. There are 96 homozygotes in GnomAd4. There are 2283 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 96 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3 link	c.93-143C>T		intron_variant	Intron 1 of 15	ENST00000375448.4	NP_036519.2	Q9UM07

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4 link	c.93-143C>T		intron_variant	Intron 1 of 15	1	NM_012387.3	ENSP00000364597.4		Q9UM07
PADI4	ENST00000375453.5 link	c.93-143C>T		intron_variant	Intron 1 of 3	2		ENSP00000364602.1		B1AQ67

Frequencies

GnomAD3 genomes

AF:

0.0314

AC:

4774

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0155

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0256

Gnomad FIN

AF:

0.0367

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0473

Gnomad OTH

AF:

0.0196

GnomAD4 exome

AF:

0.0387

AC:

16391

AN:

423756

Hom.:

409

AF XY:

0.0379

AC XY:

8405

AN XY:

221494

show subpopulations

African (AFR)

AF:

0.0153

AC:

144

AN:

9414

American (AMR)

AF:

0.0140

AC:

137

AN:

9790

Ashkenazi Jewish (ASJ)

AF:

0.0284

AC:

361

AN:

12718

East Asian (EAS)

AF:

0.000447

AC:

AN:

24594

South Asian (SAS)

AF:

0.0196

AC:

689

AN:

35078

European-Finnish (FIN)

AF:

0.0380

AC:

1176

AN:

30970

Middle Eastern (MID)

AF:

0.00920

AC:

AN:

2500

European-Non Finnish (NFE)

AF:

0.0475

AC:

13008

AN:

274016

Other (OTH)

AF:

0.0341

AC:

842

AN:

24676

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

773

1546

2318

3091

3864

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

224

336

448

560

<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:

0.0314

AC:

4777

AN:

152294

Hom.:

Cov.:

AF XY:

0.0307

AC XY:

2283

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0152

AC:

631

AN:

41564

American (AMR)

AF:

0.0155

AC:

237

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0233

AC:

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5178

South Asian (SAS)

AF:

0.0257

AC:

124

AN:

4832

European-Finnish (FIN)

AF:

0.0367

AC:

390

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0473

AC:

3217

AN:

68010

Other (OTH)

AF:

0.0194

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

234

468

703

937

1171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0303

Hom.:

Bravo

AF:

0.0286

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.83

(source)

DANN

Benign

0.48

PhyloP100

-0.64

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over