Variant 11-89402500-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

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

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

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]

NOX4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.029 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOX4	NM_016931.5 linkuse as main transcript	c.672C>T	p.Pro224=	synonymous_variant	9/18	ENST00000263317.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOX4	ENST00000263317.9 linkuse as main transcript	c.672C>T	p.Pro224=	synonymous_variant	9/18	1	NM_016931.5	P1	Q9NPH5-1

Frequencies

GnomAD3 genomes

AF:

0.000894

AC:

136

AN:

152052

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.000894

AC:

136

AN:

152170

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

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.:

Bravo

AF:

0.00102

EpiCase

AF:

0.00120

EpiControl

AF:

0.00184

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over