Genetic Variant NOX4:c.-305-806A>G (chr11-89498993-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001143837.2(NOX4):c.-305-806A>G variant causes a intron change. The variant allele was found at a frequency of 0.156 in 153,752 control chromosomes in the GnomAD database, including 2,097 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 0.16 ( 2079 hom., cov: 32)

Exomes 𝑓: 0.11 ( 18 hom. )

Consequence

NOX4
NM_001143837.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.73

Publications

14 publications found

Variant links:

COSMIC-nc: COSV73266391

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:

H3P34 (HGNC:54467): (H3 histone pseudogene 34)

H3P34 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=-0.61).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143837.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX4	NM_001143837.2		c.-305-806A>G		intron	N/A	NP_001137309.2	Q9NPH5-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H3P34	ENST00000532005.1	TSL:6	n.206A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23808

AN:

152016

Hom.:

2067

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.286

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.164

GnomAD4 exome

AF:

0.113

AC:

183

AN:

1620

Hom.:

Cov.:

AF XY:

0.109

AC XY:

AN XY:

798

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.375

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

AN:

East Asian (EAS)

AF:

0.167

AC:

AN:

South Asian (SAS)

AF:

0.189

AC:

AN:

106

European-Finnish (FIN)

AF:

0.101

AC:

142

AN:

1400

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.229

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.157

AC:

23849

AN:

152132

Hom.:

2079

Cov.:

AF XY:

0.156

AC XY:

11579

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.215

AC:

8924

AN:

41514

American (AMR)

AF:

0.137

AC:

2090

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

386

AN:

3468

East Asian (EAS)

AF:

0.286

AC:

1471

AN:

5152

South Asian (SAS)

AF:

0.142

AC:

683

AN:

4824

European-Finnish (FIN)

AF:

0.124

AC:

1311

AN:

10590

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.126

AC:

8565

AN:

68000

Other (OTH)

AF:

0.171

AC:

361

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1029

2058

3087

4116

5145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<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:

0.136

Hom.:

2743

Bravo

AF:

0.163

Asia WGS

AF:

0.222

AC:

771

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

4.9

(source)

DANN

Benign

0.61

PhyloP100

5.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over