rs689459

Variant names:

• chr16-69726719-G-C
• rs689459
• NM_000903.3:c.-280C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000903.3(NQO1):​c.-280C>G variant causes a upstream gene 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 NM_000903.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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

ACMG classification

Verdict is Benign. Variant got -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	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	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.: 32

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.: 2 AF XY: 0.00497 AC XY: 639 AN XY: 128638

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.00707

Gnomad4 ASJ exome AF: 0.000112

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000992

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000301

Gnomad4 OTH exome AF: 0.0144

GnomAD4 genome AF: 0.0435 AC: 6618 AN: 152110 Hom.: 495 Cov.: 32 AF XY: 0.0424 AC XY: 3156 AN XY: 74372

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.0144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0314

Alfa AF: 0.0329 Hom.: 31

Bravo AF: 0.0488

Asia WGS AF: 0.00664 AC: 23 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
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs689459; hg19: chr16-69760622;