rs7130284

Variant names:

• chr11-89415204-C-T
• rs7130284
• NM_016931.5:c.629+6698G>A

Variant summary

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

The NM_016931.5(NOX4):​c.629+6698G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 151,498 control chromosomes in the GnomAD database, including 1,161 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 (1161 hom., cov: 32)
• Consequence: NOX4 NM_016931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX4	NM_016931.5	c.629+6698G>A		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.629+6698G>A		intron_variant	Intron 8 of 17	1	NM_016931.5	ENSP00000263317.4

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17311 AN: 151382 Hom.: 1161 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0338

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0777

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

GnomAD4 genome AF: 0.114 AC: 17319 AN: 151498 Hom.: 1161 Cov.: 32 AF XY: 0.118 AC XY: 8737 AN XY: 74006

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.0338

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.0795

Gnomad4 OTH AF: 0.0774

Alfa AF: 0.0956 Hom.: 102

Bravo AF: 0.112

Asia WGS AF: 0.147 AC: 510 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.2
DANN	Benign	0.62

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: rs7130284; hg19: chr11-89148372;