rs10830265

Variant names:

• chr11-89379482-G-A
• rs10830265
• NM_016931.5:c.1075-5990C>T

Variant summary

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

The NM_016931.5(NOX4):​c.1075-5990C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 152,088 control chromosomes in the GnomAD database, including 797 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 0.093 (797 hom., cov: 32)
• Consequence: NOX4 NM_016931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.45
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX4	NM_016931.5	c.1075-5990C>T		intron_variant	Intron 11 of 17	ENST00000263317.9	NP_058627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX4	ENST00000263317.9	c.1075-5990C>T		intron_variant	Intron 11 of 17	1	NM_016931.5	ENSP00000263317.4

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 14140 AN: 151970 Hom.: 798 Cov.: 32

Gnomad AFR AF: 0.0826

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.0204

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0716

Gnomad OTH AF: 0.0617

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

GnomAD4 genome AF: 0.0930 AC: 14150 AN: 152088 Hom.: 797 Cov.: 32 AF XY: 0.0985 AC XY: 7326 AN XY: 74342

African (AFR) AF: 0.0826 AC: 3426 AN: 41494

American (AMR) AF: 0.147 AC: 2248 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0204 AC: 71 AN: 3472

East Asian (EAS) AF: 0.167 AC: 863 AN: 5162

South Asian (SAS) AF: 0.185 AC: 891 AN: 4820

European-Finnish (FIN) AF: 0.145 AC: 1533 AN: 10562

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

European-Non Finnish (NFE) AF: 0.0716 AC: 4866 AN: 67994

Other (OTH) AF: 0.0634 AC: 134 AN: 2112

Alfa AF: 0.0801 Hom.: 1145

Bravo AF: 0.0889

Asia WGS AF: 0.145 AC: 502 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.028
DANN	Benign	0.78
PhyloP100		-3.4
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: rs10830265; hg19: chr11-89112650;