dbSNP rs34481461: PADI4:c.1629+63C>A (chr1-17358971-C-A) – 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.1629+63C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,138,122 control chromosomes in the GnomAD database, including 17,041 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 0.14 ( 1780 hom., cov: 31)

Exomes 𝑓: 0.17 ( 15261 hom. )

Consequence

PADI4
NM_012387.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.795

Publications

5 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 (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3 link	c.1629+63C>A		intron_variant	Intron 14 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.1629+63C>A		intron_variant	Intron 14 of 15	1	NM_012387.3	ENSP00000364597.4		Q9UM07
PADI4	ENST00000467001.1 link	n.*122C>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21142

AN:

152084

Hom.:

1786

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0618

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.100

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.175

GnomAD4 exome

AF:

0.169

AC:

166277

AN:

985918

Hom.:

15261

AF XY:

0.171

AC XY:

86169

AN XY:

504190

show subpopulations

African (AFR)

AF:

0.0552

AC:

1258

AN:

22802

American (AMR)

AF:

0.131

AC:

4013

AN:

30704

Ashkenazi Jewish (ASJ)

AF:

0.302

AC:

6706

AN:

22172

East Asian (EAS)

AF:

0.267

AC:

9343

AN:

35044

South Asian (SAS)

AF:

0.207

AC:

14293

AN:

69178

European-Finnish (FIN)

AF:

0.105

AC:

5208

AN:

49816

Middle Eastern (MID)

AF:

0.275

AC:

1323

AN:

4814

European-Non Finnish (NFE)

AF:

0.164

AC:

116072

AN:

707182

Other (OTH)

AF:

0.182

AC:

8061

AN:

44206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

7059

14118

21177

28236

35295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3372

6744

10116

13488

16860

<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:

0.139

AC:

21135

AN:

152204

Hom.:

1780

Cov.:

AF XY:

0.136

AC XY:

10118

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0618

AC:

2567

AN:

41558

American (AMR)

AF:

0.132

AC:

2013

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

1041

AN:

3466

East Asian (EAS)

AF:

0.274

AC:

1416

AN:

5166

South Asian (SAS)

AF:

0.206

AC:

993

AN:

4810

European-Finnish (FIN)

AF:

0.100

AC:

1064

AN:

10618

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.167

AC:

11386

AN:

67992

Other (OTH)

AF:

0.173

AC:

365

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

920

1841

2761

3682

4602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<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:

0.145

Hom.:

215

Bravo

AF:

0.141

Asia WGS

AF:

0.204

AC:

709

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

6.1

(source)

DANN

Benign

0.74

PhyloP100

0.80

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