dbSNP rs34755915: NQO1:c.303+20G>A (chr16-69718103-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000903.3(NQO1):c.303+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,613,700 control chromosomes in the GnomAD database, including 193 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 0.0089 ( 12 hom., cov: 32)

Exomes 𝑓: 0.013 ( 181 hom. )

Consequence

NQO1
NM_000903.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.54

Publications

2 publications found

Variant links:

Genes affected

NQO1 (HGNC:2874): (NAD(P)H quinone dehydrogenase 1) This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase. This FAD-binding protein forms homodimers and reduces quinones to hydroquinones. This protein's enzymatic activity prevents the one electron reduction of quinones that results in the production of radical species. Mutations in this gene have been associated with tardive dyskinesia (TD), an increased risk of hematotoxicity after exposure to benzene, and susceptibility to various forms of cancer. Altered expression of this protein has been seen in many tumors and is also associated with Alzheimer's disease (AD). Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

NQO1 links:

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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=-0.81).

BS1

Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0133 (19364/1461336) while in subpopulation NFE AF = 0.0161 (17936/1111710). AF 95% confidence interval is 0.0159. There are 181 homozygotes in GnomAdExome4. There are 9466 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
NQO1	NM_000903.3 link	c.303+20G>A	intron_variant	Intron 3 of 5	ENST00000320623.10	NP_000894.1
NQO1	NM_001025433.2 link	c.303+20G>A	intron_variant	Intron 3 of 4		NP_001020604.1
NQO1	NM_001025434.2 link	c.303+20G>A	intron_variant	Intron 3 of 4		NP_001020605.1
NQO1	NM_001286137.2 link	c.303+20G>A	intron_variant	Intron 3 of 3		NP_001273066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NQO1	ENST00000320623.10 link	c.303+20G>A		intron_variant	Intron 3 of 5	1	NM_000903.3	ENSP00000319788.5

Frequencies

GnomAD3 genomes

AF:

0.00895

AC:

1363

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00268

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00555

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0157

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00879

AC:

2205

AN:

250744

AF XY:

0.00922

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.00383

Gnomad ASJ exome

AF:

0.00996

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00555

Gnomad NFE exome

AF:

0.0155

Gnomad OTH exome

AF:

0.00637

GnomAD4 exome

AF:

0.0133

AC:

19364

AN:

1461336

Hom.:

181

Cov.:

AF XY:

0.0130

AC XY:

9466

AN XY:

727006

show subpopulations

African (AFR)

AF:

0.00206

AC:

AN:

33456

American (AMR)

AF:

0.00361

AC:

161

AN:

44620

Ashkenazi Jewish (ASJ)

AF:

0.00900

AC:

235

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00109

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00491

AC:

262

AN:

53400

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0161

AC:

17936

AN:

1111710

Other (OTH)

AF:

0.00999

AC:

603

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1016

2031

3047

4062

5078

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.00895

AC:

1363

AN:

152364

Hom.:

Cov.:

AF XY:

0.00821

AC XY:

612

AN XY:

74514

show subpopulations

African (AFR)

AF:

0.00267

AC:

111

AN:

41586

American (AMR)

AF:

0.00490

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00950

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00555

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0157

AC:

1071

AN:

68038

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

139

208

278

347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0128

Hom.:

Bravo

AF:

0.00867

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.0

(source)

DANN

Benign

0.37

PhyloP100

2.5

Mutation Taster

=100/0

polymorphism

(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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over