Variant rs1748020 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012387.3(PADI4):c.824C>T(p.Ser275Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0512 in 1,613,608 control chromosomes in the GnomAD database, including 2,467 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.060 ( 335 hom., cov: 32)

Exomes 𝑓: 0.050 ( 2132 hom. )

Consequence

PADI4
NM_012387.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.113

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002763629).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI4	NM_012387.3 linkuse as main transcript	c.824C>T	p.Ser275Phe	missense_variant	7/16	ENST00000375448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI4	ENST00000375448.4 linkuse as main transcript	c.824C>T	p.Ser275Phe	missense_variant	7/16	1	NM_012387.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0604

AC:

9187

AN:

152142

Hom.:

332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0971

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0303

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0261

Gnomad FIN

AF:

0.0596

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0542

Gnomad OTH

AF:

0.0455

GnomAD3 exomes

AF:

0.0425

AC:

10686

AN:

251166

Hom.:

315

AF XY:

0.0414

AC XY:

5616

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.100

Gnomad AMR exome

AF:

0.0149

Gnomad ASJ exome

AF:

0.0338

Gnomad EAS exome

AF:

0.000816

Gnomad SAS exome

AF:

0.0220

Gnomad FIN exome

AF:

0.0581

Gnomad NFE exome

AF:

0.0533

Gnomad OTH exome

AF:

0.0336

GnomAD4 exome

AF:

0.0502

AC:

73410

AN:

1461348

Hom.:

2132

Cov.:

AF XY:

0.0491

AC XY:

35686

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.0996

Gnomad4 AMR exome

AF:

0.0163

Gnomad4 ASJ exome

AF:

0.0342

Gnomad4 EAS exome

AF:

0.000730

Gnomad4 SAS exome

AF:

0.0213

Gnomad4 FIN exome

AF:

0.0593

Gnomad4 NFE exome

AF:

0.0544

Gnomad4 OTH exome

AF:

0.0472

GnomAD4 genome

AF:

0.0604

AC:

9197

AN:

152260

Hom.:

335

Cov.:

AF XY:

0.0589

AC XY:

4385

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0971

Gnomad4 AMR

AF:

0.0302

Gnomad4 ASJ

AF:

0.0297

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0263

Gnomad4 FIN

AF:

0.0596

Gnomad4 NFE

AF:

0.0542

Gnomad4 OTH

AF:

0.0450

Alfa

AF:

0.0497

Hom.:

521

Bravo

AF:

0.0600

TwinsUK

AF:

0.0593

AC:

220

ALSPAC

AF:

0.0581

AC:

224

ESP6500AA

AF:

0.103

AC:

456

ESP6500EA

AF:

0.0530

AC:

456

ExAC

AF:

0.0456

AC:

5534

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0497

EpiControl

AF:

0.0474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Benign

0.021

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.059

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.091

Sift

Uncertain

0.025

Sift4G

Benign

0.081

Polyphen

0.92

Vest4

0.30

MPC

0.49

ClinPred

0.038

GERP RS

4.6

Varity_R

0.29

gMVP

0.31

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over