Variant rs34688635 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_007052.5(NOX1):c.1078G>A(p.Asp360Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0244 in 1,209,782 control chromosomes in the GnomAD database, including 300 homozygotes. There are 9,414 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.020 ( 22 hom., 671 hem., cov: 24)

Exomes 𝑓: 0.025 ( 278 hom. 8743 hem. )

Consequence

NOX1
NM_007052.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.27

Variant links:

Genes affected

NOX1 (HGNC:7889): (NADPH oxidase 1) This gene encodes a member of the NADPH oxidase family of enzymes responsible for the catalytic one-electron transfer of oxygen to generate superoxide or hydrogen peroxide. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2012]

NOX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031481355).

BP6

Variant X-100850206-C-T is Benign according to our data. Variant chrX-100850206-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0195 (2187/111968) while in subpopulation NFE AF= 0.028 (1489/53193). AF 95% confidence interval is 0.0268. There are 22 homozygotes in gnomad4. There are 671 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOX1	NM_007052.5 link	c.1078G>A	p.Asp360Asn	missense_variant	9/13	ENST00000372966.8	NP_008983.2	Q9Y5S8-1
NOX1	NM_001271815.2 link	c.967G>A	p.Asp323Asn	missense_variant	8/12		NP_001258744.1	Q9Y5S8A6NGA6Q1ZYL4
NOX1	NM_013955.3 link	c.1078G>A	p.Asp360Asn	missense_variant	9/12		NP_039249.1	Q9Y5S8-3
NOX1	XM_017029407.3 link	c.760G>A	p.Asp254Asn	missense_variant	7/11		XP_016884896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOX1	ENST00000372966.8 link	c.1078G>A	p.Asp360Asn	missense_variant	9/13	1	NM_007052.5	ENSP00000362057.3		Q9Y5S8-1
NOX1	ENST00000372964.5 link	c.477-6759G>A		intron_variant		2		ENSP00000362055.1		Q5H9D4

Frequencies

GnomAD3 genomes

AF:

0.0196

AC:

2188

AN:

111915

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

671

AN XY:

34079

show subpopulations

Gnomad AFR

AF:

0.00341

Gnomad AMI

AF:

0.0264

Gnomad AMR

AF:

0.0157

Gnomad ASJ

AF:

0.0136

Gnomad EAS

AF:

0.000279

Gnomad SAS

AF:

0.00408

Gnomad FIN

AF:

0.0538

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0280

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0191

AC:

3502

AN:

183233

Hom.:

AF XY:

0.0184

AC XY:

1244

AN XY:

67697

show subpopulations

Gnomad AFR exome

AF:

0.00312

Gnomad AMR exome

AF:

0.00828

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00483

Gnomad FIN exome

AF:

0.0501

Gnomad NFE exome

AF:

0.0261

Gnomad OTH exome

AF:

0.0248

GnomAD4 exome

AF:

0.0249

AC:

27317

AN:

1097814

Hom.:

278

Cov.:

AF XY:

0.0241

AC XY:

8743

AN XY:

363202

show subpopulations

Gnomad4 AFR exome

AF:

0.00246

Gnomad4 AMR exome

AF:

0.00940

Gnomad4 ASJ exome

AF:

0.0124

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00588

Gnomad4 FIN exome

AF:

0.0506

Gnomad4 NFE exome

AF:

0.0276

Gnomad4 OTH exome

AF:

0.0227

GnomAD4 genome

AF:

0.0195

AC:

2187

AN:

111968

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

671

AN XY:

34142

show subpopulations

Gnomad4 AFR

AF:

0.00340

Gnomad4 AMR

AF:

0.0157

Gnomad4 ASJ

AF:

0.0136

Gnomad4 EAS

AF:

0.000280

Gnomad4 SAS

AF:

0.00409

Gnomad4 FIN

AF:

0.0538

Gnomad4 NFE

AF:

0.0280

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.0246

Hom.:

1063

Bravo

AF:

0.0164

TwinsUK

AF:

0.0243

AC:

ALSPAC

AF:

0.0249

AC:

ESP6500AA

AF:

0.00417

AC:

ESP6500EA

AF:

0.0288

AC:

194

ExAC

AF:

0.0180

AC:

2183

EpiCase

AF:

0.0272

EpiControl

AF:

0.0236

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.80

D;.;.

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

D;D;D

MetaRNN

Benign

0.031

T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.9

L;.;L

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-4.4

D;D;D

REVEL

Uncertain

0.41

Sift

Benign

0.042

D;T;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.45

B;B;B

Vest4

0.18

MPC

0.090

ClinPred

0.031

GERP RS

3.9

Varity_R

0.49

gMVP

0.59

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over