dbSNP rs1369953: NOX4:c.-364-2122G>C (chr11-89548817-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_001143837.2(NOX4):c.-364-2122G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,022 control chromosomes in the GnomAD database, including 9,871 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 0.36 ( 9871 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

NOX4
NM_001143837.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00200

Publications

2 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:

ENSG00000255429 (HGNC:):

ENSG00000255429 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 = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX4	NM_001143837.2 link	c.-364-2122G>C		intron_variant	Intron 1 of 20		NP_001137309.2	Q9NPH5-8B3KQ17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000255429	ENST00000528319.1 link	n.173-2122G>C		intron_variant	Intron 1 of 1	5
ENSG00000279045	ENST00000624036.1 link	n.-22G>C		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54330

AN:

151900

Hom.:

9859

Cov.:

show subpopulations

Gnomad AFR

AF:

0.380

Gnomad AMI

AF:

0.428

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.380

Gnomad OTH

AF:

0.360

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.358

AC:

54380

AN:

152022

Hom.:

9871

Cov.:

AF XY:

0.349

AC XY:

25906

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.379

AC:

15731

AN:

41452

American (AMR)

AF:

0.296

AC:

4514

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1097

AN:

3468

East Asian (EAS)

AF:

0.338

AC:

1739

AN:

5152

South Asian (SAS)

AF:

0.348

AC:

1680

AN:

4826

European-Finnish (FIN)

AF:

0.237

AC:

2503

AN:

10578

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.380

AC:

25830

AN:

67954

Other (OTH)

AF:

0.367

AC:

776

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1797

3594

5390

7187

8984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.376

Hom.:

1317

Bravo

AF:

0.360

Asia WGS

AF:

0.374

AC:

1300

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

1.6

(source)

DANN

Benign

0.69

PhyloP100

0.0020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over