rs317191

Variant names:

• chr11-89357648-C-T
• rs317191
• NM_016931.5:c.1136-2605G>A

Variant summary

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

The NM_016931.5(NOX4):​c.1136-2605G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 151,878 control chromosomes in the GnomAD database, including 8,345 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 0.24 (8345 hom., cov: 32)
• Consequence: NOX4 NM_016931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125
• Publications: 4 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 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.1136-2605G>A		intron	N/A	NP_058627.2	Q9NPH5-1
	NOX4	NM_001291927.1		c.1199-2605G>A		intron	N/A	NP_001278856.1	Q9NPH5
	NOX4	NM_001143837.2		c.1064-2605G>A		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.1136-2605G>A		intron	N/A	ENSP00000263317.4	Q9NPH5-1
	NOX4	ENST00000534731.5	TSL:1	c.1136-2605G>A		intron	N/A	ENSP00000436892.1	Q9NPH5-6
	NOX4	ENST00000525196.5	TSL:1	c.630-17477G>A		intron	N/A	ENSP00000436716.1	E9PI95

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36567 AN: 151760 Hom.: 8304 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0722

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.241 AC: 36663 AN: 151878 Hom.: 8345 Cov.: 32 AF XY: 0.241 AC XY: 17900 AN XY: 74204

African (AFR) AF: 0.601 AC: 24866 AN: 41396

American (AMR) AF: 0.208 AC: 3172 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3466

East Asian (EAS) AF: 0.162 AC: 833 AN: 5150

South Asian (SAS) AF: 0.180 AC: 867 AN: 4818

European-Finnish (FIN) AF: 0.140 AC: 1468 AN: 10512

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0722 AC: 4909 AN: 67972

Other (OTH) AF: 0.167 AC: 353 AN: 2108

Alfa AF: 0.110 Hom.: 769

Bravo AF: 0.258

Asia WGS AF: 0.174 AC: 606 AN: 3476

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	0.28
PhyloP100		-0.13
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs317191;

hg19: chr11-89090816;