Variant 1-17336167-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_012387.3(PADI4):c.349T>C(p.Leu117Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,607,184 control chromosomes in the GnomAD database, including 353,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign,association (no stars).

Frequency

Genomes: 𝑓 0.64 ( 30890 hom., cov: 32)

Exomes 𝑓: 0.66 ( 322229 hom. )

Consequence

PADI4
NM_012387.3 synonymous

Scores

Clinical Significance

Benign; association no assertion criteria provided B:1O:1

Conservation

PhyloP100: 0.249

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-17336167-T-C is Benign according to our data. Variant chr1-17336167-T-C is described in ClinVar as [Benign, association]. Clinvar id is 972894.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.249 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 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.349T>C	p.Leu117Leu	synonymous_variant	4/16	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.349T>C	p.Leu117Leu	synonymous_variant	4/16	1	NM_012387.3	ENSP00000364597.4		Q9UM07

Frequencies

GnomAD3 genomes

AF:

0.635

AC:

96480

AN:

151842

Hom.:

30885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.574

Gnomad AMI

AF:

0.703

Gnomad AMR

AF:

0.598

Gnomad ASJ

AF:

0.671

Gnomad EAS

AF:

0.641

Gnomad SAS

AF:

0.587

Gnomad FIN

AF:

0.686

Gnomad MID

AF:

0.621

Gnomad NFE

AF:

0.675

Gnomad OTH

AF:

0.601

GnomAD3 exomes

AF:

0.632

AC:

158374

AN:

250564

Hom.:

50727

AF XY:

0.635

AC XY:

86035

AN XY:

135422

show subpopulations

Gnomad AFR exome

AF:

0.572

Gnomad AMR exome

AF:

0.532

Gnomad ASJ exome

AF:

0.655

Gnomad EAS exome

AF:

0.627

Gnomad SAS exome

AF:

0.573

Gnomad FIN exome

AF:

0.680

Gnomad NFE exome

AF:

0.676

Gnomad OTH exome

AF:

0.637

GnomAD4 exome

AF:

0.663

AC:

964792

AN:

1455226

Hom.:

322229

Cov.:

AF XY:

0.661

AC XY:

479011

AN XY:

724410

show subpopulations

Gnomad4 AFR exome

AF:

0.570

Gnomad4 AMR exome

AF:

0.544

Gnomad4 ASJ exome

AF:

0.662

Gnomad4 EAS exome

AF:

0.642

Gnomad4 SAS exome

AF:

0.578

Gnomad4 FIN exome

AF:

0.677

Gnomad4 NFE exome

AF:

0.679

Gnomad4 OTH exome

AF:

0.642

GnomAD4 genome

AF:

0.635

AC:

96521

AN:

151958

Hom.:

30890

Cov.:

AF XY:

0.635

AC XY:

47165

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.574

Gnomad4 AMR

AF:

0.597

Gnomad4 ASJ

AF:

0.671

Gnomad4 EAS

AF:

0.641

Gnomad4 SAS

AF:

0.585

Gnomad4 FIN

AF:

0.686

Gnomad4 NFE

AF:

0.675

Gnomad4 OTH

AF:

0.594

Alfa

AF:

0.662

Hom.:

65244

Bravo

AF:

0.624

Asia WGS

AF:

0.567

AC:

1971

AN:

3478

EpiCase

AF:

0.665

EpiControl

AF:

0.661

ClinVar

Significance: Benign; association

Submissions summary: Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PADI4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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). -

Rheumatoid arthritis;C5441745:Abnormal pulmonary interstitial morphology

Other:1

association, no assertion criteria provided

case-control

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Feb 01, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.8

DANN

Benign

0.65

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