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11-89402500-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_016931.5(NOX4):c.672C>T(p.Pro224=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,611,256 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00089 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

NOX4
NM_016931.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0290
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 Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
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=-0.52).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-89402500-G-A is Benign according to our data. Variant chr11-89402500-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 722792.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=0.029 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NOX4NM_016931.5 linkuse as main transcriptc.672C>T p.Pro224= synonymous_variant 9/18 ENST00000263317.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NOX4ENST00000263317.9 linkuse as main transcriptc.672C>T p.Pro224= synonymous_variant 9/181 NM_016931.5 P1Q9NPH5-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000894
AC:
136
AN:
152052
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.000577
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00150
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.000804
AC:
199
AN:
247422
Hom.:
1
AF XY:
0.000814
AC XY:
109
AN XY:
133888
show subpopulations
Gnomad AFR exome
AF:
0.0000629
Gnomad AMR exome
AF:
0.000708
Gnomad ASJ exome
AF:
0.000306
Gnomad EAS exome
AF:
0.0000549
Gnomad SAS exome
AF:
0.000167
Gnomad FIN exome
AF:
0.0000931
Gnomad NFE exome
AF:
0.00139
Gnomad OTH exome
AF:
0.00117
GnomAD4 exome
AF:
0.00121
AC:
1762
AN:
1459086
Hom.:
1
Cov.:
31
AF XY:
0.00126
AC XY:
912
AN XY:
725812
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.000838
Gnomad4 ASJ exome
AF:
0.000231
Gnomad4 EAS exome
AF:
0.0000505
Gnomad4 SAS exome
AF:
0.000152
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.00147
Gnomad4 OTH exome
AF:
0.00105
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000894
AC:
136
AN:
152170
Hom.:
0
Cov.:
32
AF XY:
0.000672
AC XY:
50
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.000577
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00150
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00138
Hom.:
0
Bravo
AF:
0.00102
EpiCase
AF:
0.00120
EpiControl
AF:
0.00184

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeApr 06, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
Cadd
Benign
6.7
Dann
Benign
0.51

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: rs140381222; hg19: chr11-89135668; API