rs957140

Positions:

• chr11-89468459-G-A

Variant summary

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

The ENST00000263317.9(NOX4):​c.154-16564C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,958 control chromosomes in the GnomAD database, including 12,488 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 0.40 (12488 hom., cov: 32)
• Consequence: NOX4 ENST00000263317.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOX4	NM_016931.5	c.154-16564C>T		intron_variant		ENST00000263317.9	NP_058627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOX4	ENST00000263317.9	c.154-16564C>T		intron_variant		1	NM_016931.5	ENSP00000263317	P1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60599 AN: 151838 Hom.: 12480 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.399 AC: 60626 AN: 151958 Hom.: 12488 Cov.: 32 AF XY: 0.402 AC XY: 29848 AN XY: 74254

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.431

Alfa AF: 0.424 Hom.: 8397

Bravo AF: 0.405

Asia WGS AF: 0.445 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.54

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: rs957140; hg19: chr11-89201627;