rs585197

Positions:

• chr11-89494453-G-A
• chr11-89494453-G-T

Variant summary

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

The NM_001143837.2(NOX4):​c.-114-2234C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,016 control chromosomes in the GnomAD database, including 34,078 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 0.65 (34078 hom., cov: 32)
• Consequence: NOX4 NM_001143837.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOX4	NM_001143837.2	c.-114-2234C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOX4	ENST00000527956.5	c.-114-2234C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98419 AN: 151898 Hom.: 34071 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.677

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

GnomAD4 genome AF: 0.648 AC: 98467 AN: 152016 Hom.: 34078 Cov.: 32 AF XY: 0.637 AC XY: 47332 AN XY: 74298

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.811

Gnomad4 OTH AF: 0.680

Alfa AF: 0.762 Hom.: 17923

Bravo AF: 0.632

Asia WGS AF: 0.571 AC: 1985 AN: 3474

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	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs585197; hg19: chr11-89227621;