rs1369953

Positions:

• chr11-89548817-C-G

Variant summary

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

The NM_001143837.2(NOX4):​c.-364-2122G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,022 control chromosomes in the GnomAD database, including 9,871 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 0.36 (9871 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: NOX4 NM_001143837.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200

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]

ENSG00000255429 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOX4	NM_001143837.2	c.-364-2122G>C		intron_variant			NP_001137309.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000255429	ENST00000528319.1	n.173-2122G>C		intron_variant		5
ENSG00000279045	ENST00000624036.1	n.-22G>C		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54330 AN: 151900 Hom.: 9859 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.360

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.358 AC: 54380 AN: 152022 Hom.: 9871 Cov.: 32 AF XY: 0.349 AC XY: 25906 AN XY: 74298

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.367

Alfa AF: 0.376 Hom.: 1317

Bravo AF: 0.360

Asia WGS AF: 0.374 AC: 1300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1369953; hg19: chr11-89281985;