dbSNP rs41265995: PADI4:p.Gly242Ser (chr1-17342014-G-A) – 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.724G>A(p.Gly242Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 1,613,816 control chromosomes in the GnomAD database, including 421 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.015 ( 32 hom., cov: 32)

Exomes 𝑓: 0.021 ( 389 hom. )

Consequence

PADI4
NM_012387.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.86

Publications

8 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 (MetaRNN=0.0074054897).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0151 (2301/152210) while in subpopulation NFE AF = 0.0241 (1637/67998). AF 95% confidence interval is 0.0231. There are 32 homozygotes in GnomAd4. There are 1077 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3 link	c.724G>A	p.Gly242Ser	missense_variant	Exon 7 of 16	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4 link	c.724G>A	p.Gly242Ser	missense_variant	Exon 7 of 16	1	NM_012387.3	ENSP00000364597.4

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2302

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00425

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00793

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.0239

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0241

Gnomad OTH

AF:

0.0144

GnomAD2 exomes

AF:

0.0159

AC:

4004

AN:

251338

AF XY:

0.0164

show subpopulations

Gnomad AFR exome

AF:

0.00431

Gnomad AMR exome

AF:

0.00735

Gnomad ASJ exome

AF:

0.00526

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0225

Gnomad NFE exome

AF:

0.0228

Gnomad OTH exome

AF:

0.0196

GnomAD4 exome

AF:

0.0212

AC:

30928

AN:

1461606

Hom.:

389

Cov.:

AF XY:

0.0213

AC XY:

15519

AN XY:

727146

show subpopulations

African (AFR)

AF:

0.00370

AC:

124

AN:

33476

American (AMR)

AF:

0.00805

AC:

360

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00681

AC:

178

AN:

26134

East Asian (EAS)

AF:

0.000151

AC:

AN:

39692

South Asian (SAS)

AF:

0.0151

AC:

1304

AN:

86246

European-Finnish (FIN)

AF:

0.0204

AC:

1089

AN:

53418

Middle Eastern (MID)

AF:

0.0156

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0239

AC:

26534

AN:

1111772

Other (OTH)

AF:

0.0206

AC:

1243

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

1480

2960

4440

5920

7400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

958

1916

2874

3832

4790

<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:

0.0151

AC:

2301

AN:

152210

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

1077

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.00424

AC:

176

AN:

41540

American (AMR)

AF:

0.00792

AC:

121

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.0114

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0239

AC:

254

AN:

10606

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0241

AC:

1637

AN:

67998

Other (OTH)

AF:

0.0142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

111

221

332

442

553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0192

Hom.:

Bravo

AF:

0.0130

TwinsUK

AF:

0.0221

AC:

ALSPAC

AF:

0.0221

AC:

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.0240

AC:

206

ExAC

AF:

0.0170

AC:

2059

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0217

EpiControl

AF:

0.0218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

Eigen

Benign

0.021

Eigen_PC

Benign

-0.063

FATHMM_MKL

Benign

0.47

MetaRNN

Benign

0.0074

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

1.9

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.9

REVEL

Benign

0.10

Sift

Benign

0.45

Sift4G

Benign

0.69

Polyphen

0.94

Vest4

0.051

MPC

0.33

ClinPred

0.029

GERP RS

4.0

Varity_R

0.20

gMVP

0.29

Mutation Taster

=67/33

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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