Variant 1-17331097-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_012387.3(PADI4):c.221T>C(p.Val74Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00111 in 1,612,070 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V74L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0061 ( 7 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 11 hom. )

Consequence

PADI4
NM_012387.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.21

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 (MetaRNN=0.008436352).

BP6

Variant 1-17331097-T-C is Benign according to our data. Variant chr1-17331097-T-C is described in ClinVar as [Benign]. Clinvar id is 711266.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00607 (924/152120) while in subpopulation AFR AF= 0.0201 (836/41496). AF 95% confidence interval is 0.019. There are 7 homozygotes in gnomad4. There are 450 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI4	NM_012387.3 linkuse as main transcript	c.221T>C	p.Val74Ala	missense_variant	2/16	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.221T>C	p.Val74Ala	missense_variant	2/16	1	NM_012387.3	ENSP00000364597.4		Q9UM07
PADI4	ENST00000375453.5 linkuse as main transcript	c.221T>C	p.Val74Ala	missense_variant	2/4	2		ENSP00000364602.1		B1AQ67

Frequencies

GnomAD3 genomes

AF:

0.00609

AC:

925

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0202

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00420

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00163

AC:

405

AN:

249002

Hom.:

AF XY:

0.00130

AC XY:

175

AN XY:

134610

show subpopulations

Gnomad AFR exome

AF:

0.0211

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.000829

GnomAD4 exome

AF:

0.000593

AC:

866

AN:

1459950

Hom.:

Cov.:

AF XY:

0.000509

AC XY:

370

AN XY:

726230

show subpopulations

Gnomad4 AFR exome

AF:

0.0190

Gnomad4 AMR exome

AF:

0.00169

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000582

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000522

Gnomad4 OTH exome

AF:

0.00148

GnomAD4 genome

AF:

0.00607

AC:

924

AN:

152120

Hom.:

Cov.:

AF XY:

0.00605

AC XY:

450

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0201

Gnomad4 AMR

AF:

0.00419

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.00685

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0195

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00194

AC:

236

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000238

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

0.0037

Eigen_PC

Benign

0.093

FATHMM_MKL

Uncertain

0.87

MetaRNN

Benign

0.0084

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.85

.;L

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.15

Sift

Benign

0.18

T;T

Sift4G

Uncertain

0.022

D;T

Polyphen

0.63

.;P

Vest4

0.22

MVP

0.31

MPC

0.29

ClinPred

0.041

GERP RS

5.6

Varity_R

0.33

gMVP

0.20

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