Variant 16-69718561-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000903.3(NQO1):c.8-27G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 1,609,374 control chromosomes in the GnomAD database, including 609,131 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 0.87 ( 57276 hom., cov: 32)

Exomes 𝑓: 0.87 ( 551855 hom. )

Consequence

NQO1
NM_000903.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0120

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
NQO1	NM_000903.3 linkuse as main transcript	c.8-27G>C	intron_variant	ENST00000320623.10	NP_000894.1
NQO1	NM_001025433.2 linkuse as main transcript	c.8-27G>C	intron_variant		NP_001020604.1
NQO1	NM_001025434.2 linkuse as main transcript	c.8-27G>C	intron_variant		NP_001020605.1
NQO1	NM_001286137.2 linkuse as main transcript	c.8-27G>C	intron_variant		NP_001273066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NQO1	ENST00000320623.10 linkuse as main transcript	c.8-27G>C		intron_variant		1	NM_000903.3	ENSP00000319788	P1	P15559-1

Frequencies

GnomAD3 genomes

AF:

0.866

AC:

131694

AN:

152046

Hom.:

57233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.863

Gnomad AMI

AF:

0.880

Gnomad AMR

AF:

0.918

Gnomad ASJ

AF:

0.850

Gnomad EAS

AF:

0.641

Gnomad SAS

AF:

0.826

Gnomad FIN

AF:

0.856

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.879

Gnomad OTH

AF:

0.867

GnomAD3 exomes

AF:

0.860

AC:

212189

AN:

246816

Hom.:

91895

AF XY:

0.856

AC XY:

114415

AN XY:

133612

show subpopulations

Gnomad AFR exome

AF:

0.864

Gnomad AMR exome

AF:

0.940

Gnomad ASJ exome

AF:

0.849

Gnomad EAS exome

AF:

0.627

Gnomad SAS exome

AF:

0.832

Gnomad FIN exome

AF:

0.863

Gnomad NFE exome

AF:

0.880

Gnomad OTH exome

AF:

0.863

GnomAD4 exome

AF:

0.869

AC:

1266503

AN:

1457210

Hom.:

551855

Cov.:

AF XY:

0.868

AC XY:

628873

AN XY:

724724

show subpopulations

Gnomad4 AFR exome

AF:

0.859

Gnomad4 AMR exome

AF:

0.937

Gnomad4 ASJ exome

AF:

0.847

Gnomad4 EAS exome

AF:

0.663

Gnomad4 SAS exome

AF:

0.832

Gnomad4 FIN exome

AF:

0.865

Gnomad4 NFE exome

AF:

0.878

Gnomad4 OTH exome

AF:

0.859

GnomAD4 genome

AF:

0.866

AC:

131790

AN:

152164

Hom.:

57276

Cov.:

AF XY:

0.863

AC XY:

64218

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.863

Gnomad4 AMR

AF:

0.918

Gnomad4 ASJ

AF:

0.850

Gnomad4 EAS

AF:

0.641

Gnomad4 SAS

AF:

0.827

Gnomad4 FIN

AF:

0.856

Gnomad4 NFE

AF:

0.879

Gnomad4 OTH

AF:

0.866

Alfa

AF:

0.854

Hom.:

6051

Bravo

AF:

0.871

Asia WGS

AF:

0.771

AC:

2686

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.4

DANN

Benign

0.35

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over