Variant 1-17308245-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012387.3(PADI4):c.23G>A(p.Arg8His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,614,030 control chromosomes in the GnomAD database, including 208 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.021 ( 105 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 103 hom. )

Consequence

PADI4
NM_012387.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.32

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003020823).

BP6

Variant 1-17308245-G-A is Benign according to our data. Variant chr1-17308245-G-A is described in ClinVar as [Benign]. Clinvar id is 777323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI4	NM_012387.3 linkuse as main transcript	c.23G>A	p.Arg8His	missense_variant	1/16	ENST00000375448.4	NP_036519.2	Q9UM07

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4 linkuse as main transcript	c.23G>A	p.Arg8His	missense_variant	1/16	1	NM_012387.3	ENSP00000364597.4		Q9UM07
PADI4	ENST00000375453.5 linkuse as main transcript	c.23G>A	p.Arg8His	missense_variant	1/4	2		ENSP00000364602.1		B1AQ67

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3163

AN:

152158

Hom.:

105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0705

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.00563

AC:

1414

AN:

251228

Hom.:

AF XY:

0.00421

AC XY:

572

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.0727

Gnomad AMR exome

AF:

0.00457

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000449

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00227

AC:

3321

AN:

1461754

Hom.:

103

Cov.:

AF XY:

0.00204

AC XY:

1482

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.0738

Gnomad4 AMR exome

AF:

0.00537

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000203

Gnomad4 OTH exome

AF:

0.00528

GnomAD4 genome

AF:

0.0208

AC:

3172

AN:

152276

Hom.:

105

Cov.:

AF XY:

0.0203

AC XY:

1511

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0705

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.00763

Hom.:

Bravo

AF:

0.0235

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0738

AC:

325

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00687

AC:

834

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 26, 2018	- -

PADI4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.20

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.30

.;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.026

Sift

Benign

0.19

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.024

.;B

Vest4

0.16

MVP

0.067

MPC

0.14

ClinPred

0.0061

GERP RS

1.9

Varity_R

0.16

gMVP

0.23

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over