Genetic Variant NOX4:c.153+10G>C (chr11-89490448-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016931.5(NOX4):c.153+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 1,587,366 control chromosomes in the GnomAD database, including 683,551 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.

Frequency

Genomes: 𝑓 0.92 ( 64572 hom., cov: 32)

Exomes 𝑓: 0.93 ( 618979 hom. )

Consequence

NOX4
NM_016931.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.19

Publications

16 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX4	NM_016931.5 link	c.153+10G>C		intron_variant	Intron 2 of 17	ENST00000263317.9	NP_058627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX4	ENST00000263317.9 link	c.153+10G>C		intron_variant	Intron 2 of 17	1	NM_016931.5	ENSP00000263317.4

Frequencies

GnomAD3 genomes

AF:

0.920

AC:

139946

AN:

152148

Hom.:

64514

Cov.:

show subpopulations

Gnomad AFR

AF:

0.940

Gnomad AMI

AF:

0.980

Gnomad AMR

AF:

0.854

Gnomad ASJ

AF:

0.947

Gnomad EAS

AF:

0.789

Gnomad SAS

AF:

0.869

Gnomad FIN

AF:

0.864

Gnomad MID

AF:

0.924

Gnomad NFE

AF:

0.942

Gnomad OTH

AF:

0.930

GnomAD2 exomes

AF:

0.896

AC:

225099

AN:

251320

AF XY:

0.900

show subpopulations

Gnomad AFR exome

AF:

0.941

Gnomad AMR exome

AF:

0.796

Gnomad ASJ exome

AF:

0.945

Gnomad EAS exome

AF:

0.786

Gnomad FIN exome

AF:

0.862

Gnomad NFE exome

AF:

0.942

Gnomad OTH exome

AF:

0.920

GnomAD4 exome

AF:

0.928

AC:

1331242

AN:

1435100

Hom.:

618979

Cov.:

AF XY:

0.927

AC XY:

663977

AN XY:

715888

show subpopulations

African (AFR)

AF:

0.943

AC:

31016

AN:

32880

American (AMR)

AF:

0.802

AC:

35812

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.943

AC:

24520

AN:

25990

East Asian (EAS)

AF:

0.756

AC:

29907

AN:

39570

South Asian (SAS)

AF:

0.883

AC:

75688

AN:

85684

European-Finnish (FIN)

AF:

0.862

AC:

46012

AN:

53356

Middle Eastern (MID)

AF:

0.922

AC:

5276

AN:

5722

European-Non Finnish (NFE)

AF:

0.945

AC:

1027724

AN:

1087694

Other (OTH)

AF:

0.929

AC:

55287

AN:

59528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

4835

9671

14506

19342

24177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20930

41860

62790

83720

104650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.920

AC:

140067

AN:

152266

Hom.:

64572

Cov.:

AF XY:

0.914

AC XY:

68026

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.940

AC:

39040

AN:

41542

American (AMR)

AF:

0.854

AC:

13066

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.947

AC:

3285

AN:

3470

East Asian (EAS)

AF:

0.790

AC:

4082

AN:

5170

South Asian (SAS)

AF:

0.869

AC:

4193

AN:

4826

European-Finnish (FIN)

AF:

0.864

AC:

9161

AN:

10600

Middle Eastern (MID)

AF:

0.925

AC:

272

AN:

294

European-Non Finnish (NFE)

AF:

0.942

AC:

64104

AN:

68034

Other (OTH)

AF:

0.931

AC:

1970

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

562

1124

1686

2248

2810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.931

Hom.:

12131

Bravo

AF:

0.921

Asia WGS

AF:

0.867

AC:

3015

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

(source)

DANN

Benign

0.43

PhyloP100

-2.2

PromoterAI

0.031

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over