rs7929532

Variant names:

• chr11-89405826-A-G
• rs7929532
• NM_016931.5:c.630-3284T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016931.5(NOX4):​c.630-3284T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0923 in 151,642 control chromosomes in the GnomAD database, including 783 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 0.092 (783 hom., cov: 31)
• Consequence: NOX4 NM_016931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 4 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX4	NM_016931.5	c.630-3284T>C		intron_variant	Intron 8 of 17	ENST00000263317.9	NP_058627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX4	ENST00000263317.9	c.630-3284T>C		intron_variant	Intron 8 of 17	1	NM_016931.5	ENSP00000263317.4

Frequencies

GnomAD3 genomes AF: 0.0924 AC: 13995 AN: 151540 Hom.: 785 Cov.: 31

Gnomad AFR AF: 0.0798

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0719

Gnomad OTH AF: 0.0635

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0923 AC: 14002 AN: 151642 Hom.: 783 Cov.: 31 AF XY: 0.0978 AC XY: 7242 AN XY: 74062

African (AFR) AF: 0.0798 AC: 3304 AN: 41380

American (AMR) AF: 0.147 AC: 2242 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3470

East Asian (EAS) AF: 0.165 AC: 844 AN: 5102

South Asian (SAS) AF: 0.187 AC: 899 AN: 4800

European-Finnish (FIN) AF: 0.144 AC: 1511 AN: 10482

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0719 AC: 4880 AN: 67898

Other (OTH) AF: 0.0634 AC: 133 AN: 2098

Alfa AF: 0.0792 Hom.: 308

Bravo AF: 0.0884

Asia WGS AF: 0.131 AC: 456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.75
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7929532; hg19: chr11-89138994;