16-69718561-C-G

Variant names:

• chr16-69718561-C-G
• rs689452
• NM_000903.3:c.8-27G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• Publications: 26 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NQO1	NM_000903.3	c.8-27G>C		intron_variant	Intron 1 of 5	ENST00000320623.10	NP_000894.1
NQO1	NM_001025433.2	c.8-27G>C		intron_variant	Intron 1 of 4		NP_001020604.1
NQO1	NM_001025434.2	c.8-27G>C		intron_variant	Intron 1 of 4		NP_001020605.1
NQO1	NM_001286137.2	c.8-27G>C		intron_variant	Intron 1 of 3		NP_001273066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NQO1	ENST00000320623.10	c.8-27G>C		intron_variant	Intron 1 of 5	1	NM_000903.3	ENSP00000319788.5

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131694 AN: 152046 Hom.: 57233 Cov.: 32

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

GnomAD2 exomes AF: 0.860 AC: 212189 AN: 246816 AF XY: 0.856

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 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.: 40 AF XY: 0.868 AC XY: 628873 AN XY: 724724

African (AFR) AF: 0.859 AC: 28668 AN: 33386

American (AMR) AF: 0.937 AC: 41604 AN: 44382

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 21931 AN: 25894

East Asian (EAS) AF: 0.663 AC: 26286 AN: 39654

South Asian (SAS) AF: 0.832 AC: 71448 AN: 85862

European-Finnish (FIN) AF: 0.865 AC: 45685 AN: 52814

Middle Eastern (MID) AF: 0.854 AC: 4268 AN: 4996

European-Non Finnish (NFE) AF: 0.878 AC: 974923 AN: 1110062

Other (OTH) AF: 0.859 AC: 51690 AN: 60160

GnomAD4 genome AF: 0.866 AC: 131790 AN: 152164 Hom.: 57276 Cov.: 32 AF XY: 0.863 AC XY: 64218 AN XY: 74392

African (AFR) AF: 0.863 AC: 35825 AN: 41532

American (AMR) AF: 0.918 AC: 14021 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 2949 AN: 3468

East Asian (EAS) AF: 0.641 AC: 3305 AN: 5156

South Asian (SAS) AF: 0.827 AC: 3989 AN: 4826

European-Finnish (FIN) AF: 0.856 AC: 9056 AN: 10584

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.879 AC: 59766 AN: 68012

Other (OTH) AF: 0.866 AC: 1825 AN: 2108

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
PhyloP100		-0.012
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs689452; hg19: chr16-69752464; COSMIC: COSV107343547;