dbSNP rs1635570: PADI4:c.1155+58C>T (chr1-17348106-C-T) – 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.1155+58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 1,122,334 control chromosomes in the GnomAD database, including 1,039 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 0.028 ( 94 hom., cov: 33)

Exomes 𝑓: 0.037 ( 945 hom. )

Consequence

PADI4
NM_012387.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.326

Publications

4 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).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0285 (4336/152330) while in subpopulation NFE AF = 0.0472 (3214/68038). AF 95% confidence interval is 0.0459. There are 94 homozygotes in GnomAd4. There are 2034 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 94 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3 link	c.1155+58C>T		intron_variant	Intron 10 of 15	ENST00000375448.4	NP_036519.2	Q9UM07

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PADI4	ENST00000375448.4 link	c.1155+58C>T	intron_variant	Intron 10 of 15	1	NM_012387.3	ENSP00000364597.4	Q9UM07
PADI4	ENST00000468945.1 link	n.272C>T	non_coding_transcript_exon_variant	Exon 2 of 2	2
PADI4	ENST00000487048.5 link	n.122+58C>T	intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.0285

AC:

4335

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00743

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0150

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.0367

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0472

Gnomad OTH

AF:

0.0182

GnomAD2 exomes

AF:

0.0288

AC:

6592

AN:

228496

AF XY:

0.0290

show subpopulations

Gnomad AFR exome

AF:

0.00743

Gnomad AMR exome

AF:

0.00933

Gnomad ASJ exome

AF:

0.0306

Gnomad EAS exome

AF:

0.000300

Gnomad FIN exome

AF:

0.0386

Gnomad NFE exome

AF:

0.0470

Gnomad OTH exome

AF:

0.0227

GnomAD4 exome

AF:

0.0373

AC:

36144

AN:

970004

Hom.:

945

Cov.:

AF XY:

0.0365

AC XY:

18296

AN XY:

501608

show subpopulations

African (AFR)

AF:

0.00743

AC:

177

AN:

23808

American (AMR)

AF:

0.00953

AC:

405

AN:

42510

Ashkenazi Jewish (ASJ)

AF:

0.0291

AC:

653

AN:

22452

East Asian (EAS)

AF:

0.000136

AC:

AN:

36640

South Asian (SAS)

AF:

0.00711

AC:

530

AN:

74592

European-Finnish (FIN)

AF:

0.0394

AC:

2022

AN:

51324

Middle Eastern (MID)

AF:

0.00748

AC:

AN:

4810

European-Non Finnish (NFE)

AF:

0.0461

AC:

30857

AN:

669724

Other (OTH)

AF:

0.0331

AC:

1459

AN:

44144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

1666

3332

4997

6663

8329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0285

AC:

4336

AN:

152330

Hom.:

Cov.:

AF XY:

0.0273

AC XY:

2034

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00741

AC:

308

AN:

41574

American (AMR)

AF:

0.0150

AC:

230

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0231

AC:

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.00518

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0367

AC:

390

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0472

AC:

3214

AN:

68038

Other (OTH)

AF:

0.0180

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

212

425

637

850

1062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0278

Hom.:

Bravo

AF:

0.0257

Asia WGS

AF:

0.00577

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

1.8

(source)

DANN

Benign

0.66

PhyloP100

-0.33

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1635570

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