rs11018628

Positions:

• chr11-89473343-T-C
• chr11-89473343-T-G

Variant summary

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

The NM_016931.5(NOX4):​c.153+17115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,052 control chromosomes in the GnomAD database, including 1,193 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 0.11 (1193 hom., cov: 32)
• Consequence: NOX4 NM_016931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOX4	NM_016931.5	c.153+17115A>G		intron_variant		ENST00000263317.9	NP_058627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOX4	ENST00000263317.9	c.153+17115A>G		intron_variant		1	NM_016931.5	ENSP00000263317	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17100 AN: 151934 Hom.: 1185 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0693

Gnomad OTH AF: 0.0831

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

GnomAD4 genome AF: 0.113 AC: 17137 AN: 152052 Hom.: 1193 Cov.: 32 AF XY: 0.117 AC XY: 8692 AN XY: 74336

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.0692

Gnomad4 OTH AF: 0.0827

Alfa AF: 0.0692 Hom.: 904

Bravo AF: 0.112

Asia WGS AF: 0.148 AC: 513 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	10
DANN	Benign	0.50

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: rs11018628; hg19: chr11-89206511;