dbSNP rs4149360: NQO2:c.7+14A>G (chr6-3006573-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000904.6(NQO2):c.7+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,588,476 control chromosomes in the GnomAD database, including 34,947 homozygotes. 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 0.16 ( 2436 hom., cov: 31)

Exomes 𝑓: 0.21 ( 32511 hom. )

Consequence

NQO2
NM_000904.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.338

Publications

22 publications found

Variant links:

Genes affected

NQO2 (HGNC:7856): (N-ribosyldihydronicotinamide:quinone dehydrogenase 2) This gene encodes a member of the thioredoxin family of enzymes. It is a cytosolic and ubiquitously expressed flavoprotein that catalyzes the two-electron reduction of quinone substrates and uses dihydronicotinamide riboside as a reducing coenzyme. Mutations in this gene have been associated with neurodegenerative diseases and several cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

NQO2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000904.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000904.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NQO2	NM_000904.6	MANE Select	c.7+14A>G	intron	N/A	NP_000895.2	P16083
NQO2	NM_001290221.2		c.7+14A>G	intron	N/A	NP_001277150.1	P16083
NQO2	NM_001318940.2		c.7+14A>G	intron	N/A	NP_001305869.1	P16083

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NQO2	ENST00000380455.11	TSL:1 MANE Select	c.7+14A>G	intron	N/A	ENSP00000369822.4	P16083
NQO2	ENST00000952452.1		c.7+14A>G	intron	N/A	ENSP00000622511.1
NQO2	ENST00000338130.7	TSL:2	c.7+14A>G	intron	N/A	ENSP00000337773.2	P16083

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24340

AN:

151554

Hom.:

2435

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0551

Gnomad AMI

AF:

0.218

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.123

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.154

GnomAD2 exomes

AF:

0.187

AC:

39489

AN:

210714

AF XY:

0.187

show subpopulations

Gnomad AFR exome

AF:

0.0573

Gnomad AMR exome

AF:

0.206

Gnomad ASJ exome

AF:

0.144

Gnomad EAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.221

Gnomad NFE exome

AF:

0.222

Gnomad OTH exome

AF:

0.183

GnomAD4 exome

AF:

0.206

AC:

296168

AN:

1436804

Hom.:

32511

Cov.:

AF XY:

0.203

AC XY:

145082

AN XY:

713480

show subpopulations

African (AFR)

AF:

0.0526

AC:

1691

AN:

32152

American (AMR)

AF:

0.193

AC:

7684

AN:

39878

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

3510

AN:

25574

East Asian (EAS)

AF:

0.100

AC:

3888

AN:

38698

South Asian (SAS)

AF:

0.114

AC:

9314

AN:

81364

European-Finnish (FIN)

AF:

0.214

AC:

11242

AN:

52490

Middle Eastern (MID)

AF:

0.111

AC:

632

AN:

5688

European-Non Finnish (NFE)

AF:

0.224

AC:

247238

AN:

1101576

Other (OTH)

AF:

0.185

AC:

10969

AN:

59384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

11500

23000

34499

45999

57499

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8420

16840

25260

33680

42100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.161

AC:

24345

AN:

151672

Hom.:

2436

Cov.:

AF XY:

0.161

AC XY:

11953

AN XY:

74100

show subpopulations

African (AFR)

AF:

0.0551

AC:

2281

AN:

41366

American (AMR)

AF:

0.179

AC:

2722

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

468

AN:

3468

East Asian (EAS)

AF:

0.123

AC:

634

AN:

5150

South Asian (SAS)

AF:

0.118

AC:

569

AN:

4812

European-Finnish (FIN)

AF:

0.221

AC:

2312

AN:

10446

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14802

AN:

67888

Other (OTH)

AF:

0.153

AC:

322

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

998

1997

2995

3994

4992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.193

Hom.:

5381

Bravo

AF:

0.155

Asia WGS

AF:

0.118

AC:

409

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.040

(source)

DANN

Benign

0.32

PhyloP100

-0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over