rs3017887

Variant names:

• chr11-89492920-A-C
• rs3017887
• NM_001143837.2:c.-114-701T>G

Your query was ambiguous. Multiple possible variants found:

• chr11-89492920-A-C
• chr11-89492920-A-T

Variant summary

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

The NM_001143837.2(NOX4):​c.-114-701T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,082 control chromosomes in the GnomAD database, including 51,171 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 0.81 (51171 hom., cov: 32)
• Consequence: NOX4 NM_001143837.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843
• Publications: 15 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX4	NM_001143837.2	c.-114-701T>G		intron_variant	Intron 3 of 20		NP_001137309.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX4	ENST00000527956.5	c.-114-701T>G		intron_variant	Intron 1 of 18	5		ENSP00000433797.1

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123055 AN: 151964 Hom.: 51162 Cov.: 32

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.930

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.835

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

GnomAD4 genome AF: 0.809 AC: 123110 AN: 152082 Hom.: 51171 Cov.: 32 AF XY: 0.806 AC XY: 59945 AN XY: 74350

African (AFR) AF: 0.626 AC: 25958 AN: 41442

American (AMR) AF: 0.730 AC: 11151 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.930 AC: 3227 AN: 3470

East Asian (EAS) AF: 0.787 AC: 4061 AN: 5162

South Asian (SAS) AF: 0.882 AC: 4255 AN: 4822

European-Finnish (FIN) AF: 0.841 AC: 8909 AN: 10598

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.924 AC: 62812 AN: 67998

Other (OTH) AF: 0.836 AC: 1758 AN: 2102

Alfa AF: 0.897 Hom.: 26774

Bravo AF: 0.789

Asia WGS AF: 0.833 AC: 2897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.94
DANN	Benign	0.57
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3017887; hg19: chr11-89226088; COSMIC: COSV107208544; COSMIC: COSV107208544;