NM_016931.5:c.153+10G>C

Variant names:

• chr11-89490448-C-G
• rs490934
• NM_016931.5:c.153+10G>C

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+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 1,587,366 control chromosomes in the GnomAD database, including 683,551 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 0.92 (64572 hom., cov: 32)
  • Exomes 𝑓: 0.93 (618979 hom.)
• Consequence: NOX4 NM_016931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 16 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.936 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+10G>C		intron	N/A	NP_058627.2
	NOX4	NM_001291927.1		c.216+10G>C		intron	N/A	NP_001278856.1
	NOX4	NM_001143837.2		c.81+10G>C		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+10G>C		intron	N/A	ENSP00000263317.4
	NOX4	ENST00000534731.5	TSL:1	c.153+10G>C		intron	N/A	ENSP00000436892.1
	NOX4	ENST00000525196.5	TSL:1	c.153+10G>C		intron	N/A	ENSP00000436716.1

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139946 AN: 152148 Hom.: 64514 Cov.: 32

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.947

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.942

Gnomad OTH AF: 0.930

GnomAD2 exomes AF: 0.896 AC: 225099 AN: 251320 AF XY: 0.900

Gnomad AFR exome AF: 0.941

Gnomad AMR exome AF: 0.796

Gnomad ASJ exome AF: 0.945

Gnomad EAS exome AF: 0.786

Gnomad FIN exome AF: 0.862

Gnomad NFE exome AF: 0.942

Gnomad OTH exome AF: 0.920

GnomAD4 exome AF: 0.928 AC: 1331242 AN: 1435100 Hom.: 618979 Cov.: 25 AF XY: 0.927 AC XY: 663977 AN XY: 715888

African (AFR) AF: 0.943 AC: 31016 AN: 32880

American (AMR) AF: 0.802 AC: 35812 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.943 AC: 24520 AN: 25990

East Asian (EAS) AF: 0.756 AC: 29907 AN: 39570

South Asian (SAS) AF: 0.883 AC: 75688 AN: 85684

European-Finnish (FIN) AF: 0.862 AC: 46012 AN: 53356

Middle Eastern (MID) AF: 0.922 AC: 5276 AN: 5722

European-Non Finnish (NFE) AF: 0.945 AC: 1027724 AN: 1087694

Other (OTH) AF: 0.929 AC: 55287 AN: 59528

GnomAD4 genome AF: 0.920 AC: 140067 AN: 152266 Hom.: 64572 Cov.: 32 AF XY: 0.914 AC XY: 68026 AN XY: 74440

African (AFR) AF: 0.940 AC: 39040 AN: 41542

American (AMR) AF: 0.854 AC: 13066 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.947 AC: 3285 AN: 3470

East Asian (EAS) AF: 0.790 AC: 4082 AN: 5170

South Asian (SAS) AF: 0.869 AC: 4193 AN: 4826

European-Finnish (FIN) AF: 0.864 AC: 9161 AN: 10600

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.942 AC: 64104 AN: 68034

Other (OTH) AF: 0.931 AC: 1970 AN: 2116

Alfa AF: 0.931 Hom.: 12131

Bravo AF: 0.921

Asia WGS AF: 0.867 AC: 3015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	12
DANN	Benign	0.43
PhyloP100		-2.2
PromoterAI		0.031	Neutral
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: rs490934; hg19: chr11-89223616;