Genetic Variant PADI4:c.*126T>C (chr1-17363881-T-C) – 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.*126T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 634,324 control chromosomes in the GnomAD database, including 94 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 0.012 ( 19 hom., cov: 33)

Exomes 𝑓: 0.014 ( 75 hom. )

Consequence

PADI4
NM_012387.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.253

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:

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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=-0.83).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0122 (1851/152336) while in subpopulation NFE AF = 0.0169 (1148/68028). AF 95% confidence interval is 0.0161. There are 19 homozygotes in GnomAd4. There are 899 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

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.*126T>C		3_prime_UTR	Exon 16 of 16	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.*126T>C		3_prime_UTR	Exon 16 of 16	ENSP00000364597.4	Q9UM07

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1852

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00326

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0151

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.0152

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0169

Gnomad OTH

AF:

0.0196

GnomAD4 exome

AF:

0.0140

AC:

6735

AN:

481988

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

3534

AN XY:

253040

show subpopulations

African (AFR)

AF:

0.00374

AC:

AN:

13108

American (AMR)

AF:

0.0156

AC:

327

AN:

20956

Ashkenazi Jewish (ASJ)

AF:

0.0190

AC:

265

AN:

13958

East Asian (EAS)

AF:

0.0000645

AC:

AN:

30992

South Asian (SAS)

AF:

0.0120

AC:

569

AN:

47258

European-Finnish (FIN)

AF:

0.0162

AC:

650

AN:

40094

Middle Eastern (MID)

AF:

0.0361

AC:

129

AN:

3576

European-Non Finnish (NFE)

AF:

0.0152

AC:

4348

AN:

285222

Other (OTH)

AF:

0.0148

AC:

396

AN:

26824

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

318

637

955

1274

1592

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:

0.0122

AC:

1851

AN:

152336

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

899

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00325

AC:

135

AN:

41588

American (AMR)

AF:

0.0150

AC:

230

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

AN:

3468

East Asian (EAS)

AF:

0.000772

AC:

AN:

5180

South Asian (SAS)

AF:

0.0110

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0152

AC:

161

AN:

10622

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0169

AC:

1148

AN:

68028

Other (OTH)

AF:

0.0194

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

176

265

353

441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0113

Hom.:

Bravo

AF:

0.0118

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

(source)

DANN

Benign

0.81

PhyloP100

0.25

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over