Genetic Variant NM_012387.3:c.1759-63C>T (chr1-17363459-C-T) – 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.1759-63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,133,392 control chromosomes in the GnomAD database, including 32,018 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 0.23 ( 4138 hom., cov: 32)

Exomes 𝑓: 0.23 ( 27880 hom. )

Consequence

PADI4
NM_012387.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.92

Publications

6 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3 link	c.1759-63C>T		intron_variant	Intron 15 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.1759-63C>T		intron_variant	Intron 15 of 15	1	NM_012387.3	ENSP00000364597.4		Q9UM07

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34937

AN:

151930

Hom.:

4134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.309

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.240

GnomAD4 exome

AF:

0.234

AC:

229819

AN:

981344

Hom.:

27880

AF XY:

0.234

AC XY:

117211

AN XY:

501578

show subpopulations

African (AFR)

AF:

0.219

AC:

5242

AN:

23966

American (AMR)

AF:

0.168

AC:

6180

AN:

36752

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

6704

AN:

21700

East Asian (EAS)

AF:

0.289

AC:

9995

AN:

34568

South Asian (SAS)

AF:

0.205

AC:

14598

AN:

71116

European-Finnish (FIN)

AF:

0.188

AC:

9358

AN:

49840

Middle Eastern (MID)

AF:

0.212

AC:

770

AN:

3630

European-Non Finnish (NFE)

AF:

0.239

AC:

166353

AN:

695804

Other (OTH)

AF:

0.242

AC:

10619

AN:

43968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

9135

18270

27405

36540

45675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4616

9232

13848

18464

23080

<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:

0.230

AC:

34966

AN:

152048

Hom.:

4138

Cov.:

AF XY:

0.226

AC XY:

16798

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.221

AC:

9164

AN:

41480

American (AMR)

AF:

0.191

AC:

2919

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

1071

AN:

3466

East Asian (EAS)

AF:

0.306

AC:

1573

AN:

5140

South Asian (SAS)

AF:

0.211

AC:

1019

AN:

4826

European-Finnish (FIN)

AF:

0.182

AC:

1929

AN:

10576

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.242

AC:

16478

AN:

67962

Other (OTH)

AF:

0.238

AC:

503

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1378

2756

4134

5512

6890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<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:

0.238

Hom.:

500

Bravo

AF:

0.233

Asia WGS

AF:

0.232

AC:

806

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.18

(source)

DANN

Benign

0.47

PhyloP100

-1.9

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over