rs1836882

Positions:

• chr11-89498993-T-C

Variant summary

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

The NM_001143837.2(NOX4):​c.-305-806A>G variant causes a intron change. The variant allele was found at a frequency of 0.156 in 153,752 control chromosomes in the GnomAD database, including 2,097 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 0.16 (2079 hom., cov: 32)
  • Exomes 𝑓: 0.11 (18 hom.)
• Consequence: NOX4 NM_001143837.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.73

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]

H3P34 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOX4	NM_001143837.2	c.-305-806A>G		intron_variant			NP_001137309.2
H3P34		n.89498993T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H3P34	ENST00000532005.1	n.206A>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23808 AN: 152016 Hom.: 2067 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.113 AC: 183 AN: 1620 Hom.: 18 Cov.: 0 AF XY: 0.109 AC XY: 87 AN XY: 798

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.157 AC: 23849 AN: 152132 Hom.: 2079 Cov.: 32 AF XY: 0.156 AC XY: 11579 AN XY: 74360

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.171

Alfa AF: 0.131 Hom.: 1819

Bravo AF: 0.163

Asia WGS AF: 0.222 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.9
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1836882; hg19: chr11-89232161; COSMIC: COSV73266391;