Variant rs689453 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_000903.3(NQO1):c.72G>A(p.Glu24Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 1,614,098 control chromosomes in the GnomAD database, including 4,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.062 ( 330 hom., cov: 32)

Exomes 𝑓: 0.071 ( 4083 hom. )

Consequence

NQO1
NM_000903.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.183

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:

NQO1 (HGNC:):

NQO1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 16-69718470-C-T is Benign according to our data. Variant chr16-69718470-C-T is described in ClinVar as [Benign]. Clinvar id is 3055562.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.183 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NQO1	NM_000903.3 linkuse as main transcript	c.72G>A	p.Glu24Glu	synonymous_variant	2/6	ENST00000320623.10	NP_000894.1	P15559-1
NQO1	NM_001025433.2 linkuse as main transcript	c.72G>A	p.Glu24Glu	synonymous_variant	2/5		NP_001020604.1	P15559-2
NQO1	NM_001025434.2 linkuse as main transcript	c.72G>A	p.Glu24Glu	synonymous_variant	2/5		NP_001020605.1	P15559-3
NQO1	NM_001286137.2 linkuse as main transcript	c.72G>A	p.Glu24Glu	synonymous_variant	2/4		NP_001273066.1	B4DLR8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NQO1	ENST00000320623.10 linkuse as main transcript	c.72G>A	p.Glu24Glu	synonymous_variant	2/6	1	NM_000903.3	ENSP00000319788.5		P15559-1

Frequencies

GnomAD3 genomes

AF:

0.0624

AC:

9497

AN:

152144

Hom.:

327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0506

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.0523

Gnomad ASJ

AF:

0.0755

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0267

Gnomad FIN

AF:

0.0694

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0763

Gnomad OTH

AF:

0.0664

GnomAD3 exomes

AF:

0.0584

AC:

14668

AN:

251314

Hom.:

527

AF XY:

0.0584

AC XY:

7929

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.0472

Gnomad AMR exome

AF:

0.0369

Gnomad ASJ exome

AF:

0.0709

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0312

Gnomad FIN exome

AF:

0.0712

Gnomad NFE exome

AF:

0.0793

Gnomad OTH exome

AF:

0.0662

GnomAD4 exome

AF:

0.0710

AC:

103772

AN:

1461836

Hom.:

4083

Cov.:

AF XY:

0.0695

AC XY:

50559

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0518

Gnomad4 AMR exome

AF:

0.0394

Gnomad4 ASJ exome

AF:

0.0756

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0305

Gnomad4 FIN exome

AF:

0.0716

Gnomad4 NFE exome

AF:

0.0784

Gnomad4 OTH exome

AF:

0.0679

GnomAD4 genome

AF:

0.0625

AC:

9515

AN:

152262

Hom.:

330

Cov.:

AF XY:

0.0609

AC XY:

4532

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0510

Gnomad4 AMR

AF:

0.0521

Gnomad4 ASJ

AF:

0.0755

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0265

Gnomad4 FIN

AF:

0.0694

Gnomad4 NFE

AF:

0.0763

Gnomad4 OTH

AF:

0.0662

Alfa

AF:

0.0742

Hom.:

827

Bravo

AF:

0.0626

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0815

EpiControl

AF:

0.0808

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NQO1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

9.6

DANN

Benign

0.55

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over