rs317191

Positions:

• chr11-89357648-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016931.5(NOX4):​c.1136-2605G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 151,878 control chromosomes in the GnomAD database, including 8,345 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 0.24 (8345 hom., cov: 32)
• Consequence: NOX4 NM_016931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOX4	NM_016931.5	c.1136-2605G>A		intron_variant		ENST00000263317.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOX4	ENST00000263317.9	c.1136-2605G>A		intron_variant		1	NM_016931.5	P1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36567 AN: 151760 Hom.: 8304 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0722

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.241 AC: 36663 AN: 151878 Hom.: 8345 Cov.: 32 AF XY: 0.241 AC XY: 17900 AN XY: 74204

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.0205

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.0722

Gnomad4 OTH AF: 0.167

Alfa AF: 0.116 Hom.: 706

Bravo AF: 0.258

Asia WGS AF: 0.174 AC: 606 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.28

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: rs317191; hg19: chr11-89090816;