11-89473343-T-C

Variant names:

• chr11-89473343-T-C
• rs11018628
• NM_016931.5:c.153+17115A>G

Variant summary

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

The NM_016931.5(NOX4):​c.153+17115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,052 control chromosomes in the GnomAD database, including 1,193 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 0.11 (1193 hom., cov: 32)
• Consequence: NOX4 NM_016931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753
• Publications: 12 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.198 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX4	NM_016931.5	MANE Select	c.153+17115A>G		intron	N/A	NP_058627.2
	NOX4	NM_001291927.1		c.216+17115A>G		intron	N/A	NP_001278856.1
	NOX4	NM_001143837.2		c.81+17115A>G		intron	N/A	NP_001137309.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX4	ENST00000263317.9	TSL:1 MANE Select	c.153+17115A>G		intron	N/A	ENSP00000263317.4
	NOX4	ENST00000534731.5	TSL:1	c.153+17115A>G		intron	N/A	ENSP00000436892.1
	NOX4	ENST00000525196.5	TSL:1	c.153+17115A>G		intron	N/A	ENSP00000436716.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17100 AN: 151934 Hom.: 1185 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0693

Gnomad OTH AF: 0.0831

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

GnomAD4 genome AF: 0.113 AC: 17137 AN: 152052 Hom.: 1193 Cov.: 32 AF XY: 0.117 AC XY: 8692 AN XY: 74336

African (AFR) AF: 0.154 AC: 6369 AN: 41472

American (AMR) AF: 0.157 AC: 2400 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3468

East Asian (EAS) AF: 0.171 AC: 879 AN: 5148

South Asian (SAS) AF: 0.208 AC: 1006 AN: 4826

European-Finnish (FIN) AF: 0.137 AC: 1446 AN: 10590

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0692 AC: 4707 AN: 67980

Other (OTH) AF: 0.0827 AC: 175 AN: 2116

Alfa AF: 0.0788 Hom.: 2515

Bravo AF: 0.112

Asia WGS AF: 0.148 AC: 513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.50
PhyloP100		0.75
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: rs11018628; hg19: chr11-89206511;