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GeneBe

11-89400338-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_016931.5(NOX4):c.888C>G(p.Ala296=) 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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.968
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-89400338-G-C is Benign according to our data. Variant chr11-89400338-G-C is described in ClinVar as [Benign]. Clinvar id is 786208.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.968 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 26 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NOX4NM_016931.5 linkuse as main transcriptc.888C>G p.Ala296= synonymous_variant 10/18 ENST00000263317.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NOX4ENST00000263317.9 linkuse as main transcriptc.888C>G p.Ala296= synonymous_variant 10/181 NM_016931.5 P1Q9NPH5-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00895
AC:
1359
AN:
151896
Hom.:
26
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.00220
AC:
548
AN:
249610
Hom.:
8
AF XY:
0.00165
AC XY:
222
AN XY:
134900
show subpopulations
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 SAS exome
AF:
0.000131
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0312
Gnomad4 AMR exome
AF:
0.000808
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000697
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.00199
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00893
AC:
1358
AN:
152014
Hom.:
26
Cov.:
32
AF XY:
0.00867
AC XY:
644
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.0313
Gnomad4 AMR
AF:
0.00283
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00664
Alfa
AF:
0.000426
Hom.:
0
Bravo
AF:
0.0101
EpiCase
AF:
0.0000550
EpiControl
AF:
0.0000596

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 02, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
Cadd
Benign
2.6
Dann
Benign
0.57

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs139363194; hg19: chr11-89133506; API