11-89447940-A-G

Variant names:

• chr11-89447940-A-G
• rs319016
• NM_016931.5:c.349+1500T>C

Variant summary

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

The NM_016931.5(NOX4):​c.349+1500T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 151,970 control chromosomes in the GnomAD database, including 33,377 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 (33377 hom., cov: 31)
• Consequence: NOX4 NM_016931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016931.5. 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_016931.5	MANE Select	c.349+1500T>C		intron	N/A	NP_058627.2	Q9NPH5-1
	NOX4	NM_001291927.1		c.412+1500T>C		intron	N/A	NP_001278856.1	Q9NPH5
	NOX4	NM_001143837.2		c.277+1500T>C		intron	N/A	NP_001137309.2	Q9NPH5-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX4	ENST00000263317.9	TSL:1 MANE Select	c.349+1500T>C		intron	N/A	ENSP00000263317.4	Q9NPH5-1
	NOX4	ENST00000534731.5	TSL:1	c.349+1500T>C		intron	N/A	ENSP00000436892.1	Q9NPH5-6
	NOX4	ENST00000525196.5	TSL:1	c.349+1500T>C		intron	N/A	ENSP00000436716.1	E9PI95

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98078 AN: 151852 Hom.: 33312 Cov.: 31

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.646 AC: 98204 AN: 151970 Hom.: 33377 Cov.: 31 AF XY: 0.648 AC XY: 48120 AN XY: 74264

African (AFR) AF: 0.863 AC: 35785 AN: 41474

American (AMR) AF: 0.675 AC: 10301 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1689 AN: 3470

East Asian (EAS) AF: 0.732 AC: 3770 AN: 5152

South Asian (SAS) AF: 0.581 AC: 2796 AN: 4816

European-Finnish (FIN) AF: 0.525 AC: 5536 AN: 10540

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.533 AC: 36236 AN: 67960

Other (OTH) AF: 0.611 AC: 1286 AN: 2106

Alfa AF: 0.559 Hom.: 12227

Bravo AF: 0.668

Asia WGS AF: 0.654 AC: 2271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.084
DANN	Benign	0.49
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs319016; hg19: chr11-89181108;