rs2164521

Variant names:

• chr11-89476817-G-A
• rs2164521
• NM_016931.5:c.153+13641C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-89476817-G-A
• chr11-89476817-G-C
• chr11-89476817-G-T

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+13641C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 151,904 control chromosomes in the GnomAD database, including 4,758 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 0.21 (4758 hom., cov: 32)
• Consequence: NOX4 NM_016931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351
• Publications: 9 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX4	NM_016931.5	c.153+13641C>T		intron_variant	Intron 2 of 17	ENST00000263317.9	NP_058627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX4	ENST00000263317.9	c.153+13641C>T		intron_variant	Intron 2 of 17	1	NM_016931.5	ENSP00000263317.4

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32531 AN: 151786 Hom.: 4746 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.214 AC: 32579 AN: 151904 Hom.: 4758 Cov.: 32 AF XY: 0.218 AC XY: 16200 AN XY: 74222

African (AFR) AF: 0.414 AC: 17120 AN: 41384

American (AMR) AF: 0.153 AC: 2332 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 648 AN: 3470

East Asian (EAS) AF: 0.205 AC: 1057 AN: 5168

South Asian (SAS) AF: 0.216 AC: 1038 AN: 4816

European-Finnish (FIN) AF: 0.218 AC: 2292 AN: 10526

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7452 AN: 67960

Other (OTH) AF: 0.202 AC: 426 AN: 2112

Alfa AF: 0.130 Hom.: 4925

Bravo AF: 0.219

Asia WGS AF: 0.227 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.28
PhyloP100		-0.35
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: rs2164521; hg19: chr11-89209985;