11-89531999-T-C

Variant names:

• chr11-89531999-T-C
• rs1836883
• NM_001143837.2:c.-306+14638A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143837.2(NOX4):​c.-306+14638A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,006 control chromosomes in the GnomAD database, including 23,352 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 0.54 (23352 hom., cov: 32)
• Consequence: NOX4 NM_001143837.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143837.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX4	NM_001143837.2		c.-306+14638A>G		intron	N/A	NP_001137309.2	Q9NPH5-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82033 AN: 151888 Hom.: 23293 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.540 AC: 82159 AN: 152006 Hom.: 23352 Cov.: 32 AF XY: 0.536 AC XY: 39836 AN XY: 74286

African (AFR) AF: 0.717 AC: 29748 AN: 41486

American (AMR) AF: 0.563 AC: 8598 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1372 AN: 3468

East Asian (EAS) AF: 0.543 AC: 2783 AN: 5126

South Asian (SAS) AF: 0.452 AC: 2175 AN: 4814

European-Finnish (FIN) AF: 0.424 AC: 4482 AN: 10572

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31175 AN: 67956

Other (OTH) AF: 0.517 AC: 1091 AN: 2110

Alfa AF: 0.488 Hom.: 58634

Bravo AF: 0.559

Asia WGS AF: 0.529 AC: 1838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.69
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1836883; hg19: chr11-89265167;