rs317148

Variant names:

• chr11-89437347-T-C
• rs317148
• NM_016931.5:c.475+3341A>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.475+3341A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,058 control chromosomes in the GnomAD database, including 27,756 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 0.58 (27756 hom., cov: 31)
• Consequence: NOX4 NM_016931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 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.475+3341A>G		intron	N/A	NP_058627.2
	NOX4	NM_001291927.1		c.538+3341A>G		intron	N/A	NP_001278856.1
	NOX4	NM_001143837.2		c.403+3341A>G		intron	N/A	NP_001137309.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX4	ENST00000263317.9	TSL:1 MANE Select	c.475+3341A>G		intron	N/A	ENSP00000263317.4
	NOX4	ENST00000534731.5	TSL:1	c.475+3341A>G		intron	N/A	ENSP00000436892.1
	NOX4	ENST00000525196.5	TSL:1	c.475+3341A>G		intron	N/A	ENSP00000436716.1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87776 AN: 151940 Hom.: 27693 Cov.: 31

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.578 AC: 87900 AN: 152058 Hom.: 27756 Cov.: 31 AF XY: 0.581 AC XY: 43157 AN XY: 74328

African (AFR) AF: 0.834 AC: 34598 AN: 41500

American (AMR) AF: 0.601 AC: 9159 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1289 AN: 3472

East Asian (EAS) AF: 0.735 AC: 3788 AN: 5154

South Asian (SAS) AF: 0.529 AC: 2553 AN: 4830

European-Finnish (FIN) AF: 0.449 AC: 4745 AN: 10566

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29941 AN: 67972

Other (OTH) AF: 0.539 AC: 1138 AN: 2110

Alfa AF: 0.486 Hom.: 61970

Bravo AF: 0.601

Asia WGS AF: 0.629 AC: 2185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.27
DANN	Benign	0.64
PhyloP100		-1.3
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: rs317148; hg19: chr11-89170515;