X-100850206-C-T

Variant names:

• chrX-100850206-C-T
• rs34688635
• NM_007052.5:c.1078G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.27
• Publications: 13 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.031481355).
• 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 the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007052.5. 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
	NOX1	NM_007052.5	MANE Select	c.1078G>A	p.Asp360Asn	missense	Exon 9 of 13	NP_008983.2	Q9Y5S8-1
	NOX1	NM_001271815.2		c.967G>A	p.Asp323Asn	missense	Exon 8 of 12	NP_001258744.1	A6NGA6
	NOX1	NM_013955.3		c.1078G>A	p.Asp360Asn	missense	Exon 9 of 12	NP_039249.1	Q9Y5S8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOX1	ENST00000372966.8	TSL:1 MANE Select	c.1078G>A	p.Asp360Asn	missense	Exon 9 of 13	ENSP00000362057.3	Q9Y5S8-1
	NOX1	ENST00000372960.8	TSL:1	c.967G>A	p.Asp323Asn	missense	Exon 8 of 12	ENSP00000362051.4	A6NGA6
	NOX1	ENST00000217885.5	TSL:1	c.1078G>A	p.Asp360Asn	missense	Exon 9 of 12	ENSP00000217885.5	Q9Y5S8-3

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2188 AN: 111915 Hom.: 22 Cov.: 24

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

GnomAD2 exomes AF: 0.0191 AC: 3502 AN: 183233 AF XY: 0.0184

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 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.: 31 AF XY: 0.0241 AC XY: 8743 AN XY: 363202

African (AFR) AF: 0.00246 AC: 65 AN: 26396

American (AMR) AF: 0.00940 AC: 331 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 241 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.00588 AC: 318 AN: 54112

European-Finnish (FIN) AF: 0.0506 AC: 2049 AN: 40524

Middle Eastern (MID) AF: 0.0119 AC: 49 AN: 4134

European-Non Finnish (NFE) AF: 0.0276 AC: 23217 AN: 841776

Other (OTH) AF: 0.0227 AC: 1047 AN: 46083

GnomAD4 genome AF: 0.0195 AC: 2187 AN: 111968 Hom.: 22 Cov.: 24 AF XY: 0.0197 AC XY: 671 AN XY: 34142

African (AFR) AF: 0.00340 AC: 105 AN: 30868

American (AMR) AF: 0.0157 AC: 165 AN: 10507

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 36 AN: 2649

East Asian (EAS) AF: 0.000280 AC: 1 AN: 3577

South Asian (SAS) AF: 0.00409 AC: 11 AN: 2687

European-Finnish (FIN) AF: 0.0538 AC: 326 AN: 6059

Middle Eastern (MID) AF: 0.00926 AC: 2 AN: 216

European-Non Finnish (NFE) AF: 0.0280 AC: 1489 AN: 53193

Other (OTH) AF: 0.0222 AC: 34 AN: 1529

Alfa AF: 0.0232 Hom.: 1079

Bravo AF: 0.0164

TwinsUK AF: 0.0243 AC: 90

ALSPAC AF: 0.0249 AC: 72

ESP6500AA AF: 0.00417 AC: 16

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.80	D
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.3
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-4.4	D
REVEL	Uncertain	0.41
Sift	Benign	0.042	D
Sift4G	Benign	0.20	T
Polyphen		0.45	B
Vest4		0.18
MPC		0.090
ClinPred		0.031	T
GERP RS		3.9
PromoterAI		0.0041	Neutral
Varity_R		0.49
gMVP		0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34688635; hg19: chrX-100105195; COSMIC: COSV54196972;