11-89379482-G-A

Position:

• chr11-89379482-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NOX4	NM_016931.5	c.1075-5990C>T		intron_variant		ENST00000263317.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOX4	ENST00000263317.9	c.1075-5990C>T		intron_variant		1	NM_016931.5	P1

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

Gnomad4 AFR AF: 0.0826

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.0204

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.0716

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0789 Hom.: 238

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

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

LitVar

Other links and lift over

dbSNP: rs10830265; hg19: chr11-89112650;