NM_016931.5:c.888C>G

Variant names:

• chr11-89400338-G-C
• rs139363194
• NM_016931.5:c.888C>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_016931.5(NOX4):​c.888C>G​(p.Ala296Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,612,102 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0089 (26 hom., cov: 32)
  • Exomes 𝑓: 0.00084 (21 hom.)
• Consequence: NOX4 NM_016931.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.968
• Publications: 2 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 11-89400338-G-C is Benign according to our data. Variant chr11-89400338-G-C is described in ClinVar as Benign. ClinVar VariationId is 786208.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.968 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00893 (1358/152014) while in subpopulation AFR AF = 0.0313 (1297/41488). AF 95% confidence interval is 0.0298. There are 26 homozygotes in GnomAd4. There are 644 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

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.888C>G	p.Ala296Ala	synonymous	Exon 10 of 18	NP_058627.2	Q9NPH5-1
	NOX4	NM_001291927.1		c.951C>G	p.Ala317Ala	synonymous	Exon 10 of 18	NP_001278856.1	Q9NPH5
	NOX4	NM_001143837.2		c.816C>G	p.Ala272Ala	synonymous	Exon 13 of 21	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.888C>G	p.Ala296Ala	synonymous	Exon 10 of 18	ENSP00000263317.4	Q9NPH5-1
	NOX4	ENST00000534731.5	TSL:1	c.888C>G	p.Ala296Ala	synonymous	Exon 10 of 17	ENSP00000436892.1	Q9NPH5-6
	NOX4	ENST00000525196.5	TSL:1	c.629+21564C>G		intron	N/A	ENSP00000436716.1	E9PI95

Frequencies

GnomAD3 genomes AF: 0.00895 AC: 1359 AN: 151896 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00283

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00671

GnomAD2 exomes AF: 0.00220 AC: 548 AN: 249610 AF XY: 0.00165

Gnomad AFR exome AF: 0.0317

Gnomad AMR exome AF: 0.000641

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.000823

GnomAD4 exome AF: 0.000836 AC: 1220 AN: 1460088 Hom.: 21 Cov.: 33 AF XY: 0.000694 AC XY: 504 AN XY: 726292

African (AFR) AF: 0.0312 AC: 1041 AN: 33396

American (AMR) AF: 0.000808 AC: 36 AN: 44536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39588

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5748

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111040

Other (OTH) AF: 0.00199 AC: 120 AN: 60296

GnomAD4 genome AF: 0.00893 AC: 1358 AN: 152014 Hom.: 26 Cov.: 32 AF XY: 0.00867 AC XY: 644 AN XY: 74308

African (AFR) AF: 0.0313 AC: 1297 AN: 41488

American (AMR) AF: 0.00283 AC: 43 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67974

Other (OTH) AF: 0.00664 AC: 14 AN: 2108

Alfa AF: 0.000426 Hom.: 0

Bravo AF: 0.0101

EpiCase AF: 0.0000550

EpiControl AF: 0.0000596

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.6
DANN	Benign	0.57
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs139363194; hg19: chr11-89133506;