NM_016931.5:c.1408C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016931.5(NOX4):c.1408C>T(p.Arg470Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,573,164 control chromosomes in the GnomAD database, including 15 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 (★★).

Frequency

Genomes: 𝑓 0.0055 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 7 hom. )

Consequence

NOX4
NM_016931.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.936

Variant links:

Genes affected

NOX4 (HGNC:7891): (NADPH oxidase 4) This gene encodes a member of the NOX-family of enzymes that functions as the catalytic subunit the NADPH oxidase complex. The encoded protein is localized to non-phagocytic cells where it acts as an oxygen sensor and catalyzes the reduction of molecular oxygen to various reactive oxygen species (ROS). The ROS generated by this protein have been implicated in numerous biological functions including signal transduction, cell differentiation and tumor cell growth. A pseudogene has been identified on the other arm of chromosome 11. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2009]

NOX4 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=0.015197724).

BP6

Variant 11-89340101-G-A is Benign according to our data. Variant chr11-89340101-G-A is described in ClinVar as [Benign]. Clinvar id is 786601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00548 (833/152120) while in subpopulation AFR AF= 0.0187 (778/41510). AF 95% confidence interval is 0.0177. There are 8 homozygotes in gnomad4. There are 392 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX4	NM_016931.5 link	c.1408C>T	p.Arg470Cys	missense_variant	Exon 15 of 18	ENST00000263317.9	NP_058627.2	Q9NPH5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX4	ENST00000263317.9 link	c.1408C>T	p.Arg470Cys	missense_variant	Exon 15 of 18	1	NM_016931.5	ENSP00000263317.4		Q9NPH5-1

Frequencies

GnomAD3 genomes

AF:

0.00545

AC:

828

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0187

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00269

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00127

AC:

265

AN:

209308

Hom.:

AF XY:

0.000866

AC XY:

AN XY:

114338

show subpopulations

Gnomad AFR exome

AF:

0.0179

Gnomad AMR exome

AF:

0.000992

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000963

Gnomad NFE exome

AF:

0.0000201

Gnomad OTH exome

AF:

0.000628

GnomAD4 exome

AF:

0.000563

AC:

800

AN:

1421044

Hom.:

Cov.:

AF XY:

0.000468

AC XY:

331

AN XY:

706560

show subpopulations

Gnomad4 AFR exome

AF:

0.0209

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000503

Gnomad4 FIN exome

AF:

0.0000568

Gnomad4 NFE exome

AF:

0.0000219

Gnomad4 OTH exome

AF:

0.00140

GnomAD4 genome

AF:

0.00548

AC:

833

AN:

152120

Hom.:

Cov.:

AF XY:

0.00527

AC XY:

392

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0187

Gnomad4 AMR

AF:

0.00269

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.00653

ESP6500AA

AF:

0.0173

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00171

AC:

208

Asia WGS

AF:

0.000867

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Uncertain

0.68

.;.;.;.;D;.;.;.;.;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.80

T;.;T;T;T;T;.;T;T;T

MetaRNN

Benign

0.015

T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.0079

MutationAssessor

Benign

0.0

.;.;.;.;N;.;.;.;.;.

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-3.0

D;D;D;D;D;D;D;D;D;D

REVEL

Uncertain

0.31

Sift

Benign

0.20

T;T;T;T;T;T;T;T;T;T

Sift4G

Uncertain

0.059

T;T;T;T;T;T;T;D;T;D

Polyphen

0.0040, 0.37, 0.0010, 0.0030, 0.0, 0.99

.;.;B;B;B;.;.;B;B;D

Vest4

0.29

MVP

0.89

MPC

0.059

ClinPred

0.037

GERP RS

1.3

Varity_R

0.10

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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