Genetic Variant PADI4:c.1758+148G>C (chr1-17359556-G-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.1758+148G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00413 in 1,017,734 control chromosomes in the GnomAD database, including 115 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 0.017 ( 76 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 39 hom. )

Consequence

PADI4
NM_012387.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.831

Publications

1 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=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3 link	c.1758+148G>C		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.1758+148G>C		intron_variant	Intron 15 of 15	1	NM_012387.3	ENSP00000364597.4		Q9UM07

Frequencies

GnomAD3 genomes

AF:

0.0171

AC:

2604

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0587

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00752

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0153

GnomAD4 exome

AF:

0.00183

AC:

1583

AN:

865524

Hom.:

AF XY:

0.00160

AC XY:

699

AN XY:

437882

show subpopulations

African (AFR)

AF:

0.0556

AC:

1144

AN:

20586

American (AMR)

AF:

0.00570

AC:

134

AN:

23524

Ashkenazi Jewish (ASJ)

AF:

0.000429

AC:

AN:

16328

East Asian (EAS)

AF:

0.00

AC:

AN:

33910

South Asian (SAS)

AF:

0.000138

AC:

AN:

58160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40134

Middle Eastern (MID)

AF:

0.00334

AC:

AN:

2996

European-Non Finnish (NFE)

AF:

0.000179

AC:

113

AN:

630554

Other (OTH)

AF:

0.00425

AC:

167

AN:

39332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

125

187

250

312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.0172

AC:

2619

AN:

152210

Hom.:

Cov.:

AF XY:

0.0172

AC XY:

1283

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0589

AC:

2443

AN:

41510

American (AMR)

AF:

0.00751

AC:

115

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

68018

Other (OTH)

AF:

0.0151

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

128

257

385

514

642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.000142

Hom.:

Bravo

AF:

0.0191

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.17

(source)

DANN

Benign

0.15

PhyloP100

-0.83

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