dbSNP rs689459: NQO1-DT:n.109G>C (chr16-69726719-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000690354.2(NQO1-DT):n.109G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 400,226 control chromosomes in the GnomAD database, including 604 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 0.044 ( 495 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 109 hom. )

Consequence

NQO1-DT
ENST00000690354.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.115

Publications

7 publications found

Variant links:

Genes affected

NQO1-DT (HGNC:55344): (NQO1 divergent transcript)

NQO1-DT links:

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:

Genome browser will be placed here

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=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NQO1	NM_000903.3 link	c.-280C>G		upstream_gene_variant		ENST00000320623.10	NP_000894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NQO1	ENST00000320623.10 link	c.-280C>G		upstream_gene_variant		1	NM_000903.3	ENSP00000319788.5

Frequencies

GnomAD3 genomes

AF:

0.0435

AC:

6618

AN:

151992

Hom.:

497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0317

GnomAD4 exome

AF:

0.00577

AC:

1432

AN:

248116

Hom.:

109

Cov.:

AF XY:

0.00497

AC XY:

639

AN XY:

128638

show subpopulations

African (AFR)

AF:

0.151

AC:

1089

AN:

7204

American (AMR)

AF:

0.00707

AC:

AN:

8766

Ashkenazi Jewish (ASJ)

AF:

0.000112

AC:

AN:

8904

East Asian (EAS)

AF:

0.00

AC:

AN:

21220

South Asian (SAS)

AF:

0.0000992

AC:

AN:

10078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19134

Middle Eastern (MID)

AF:

0.00500

AC:

AN:

1200

European-Non Finnish (NFE)

AF:

0.000301

AC:

AN:

155894

Other (OTH)

AF:

0.0144

AC:

226

AN:

15716

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

112

168

224

280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0435

AC:

6618

AN:

152110

Hom.:

495

Cov.:

AF XY:

0.0424

AC XY:

3156

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.152

AC:

6304

AN:

41426

American (AMR)

AF:

0.0144

AC:

220

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000415

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

68024

Other (OTH)

AF:

0.0314

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

268

536

805

1073

1341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0327

Hom.:

Bravo

AF:

0.0488

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.7

(source)

DANN

Benign

0.67

PhyloP100

-0.12

PromoterAI

-0.28

Neutral

(source)

Mutation Taster

=300/0

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

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