chr16-69718561-C-G

Position:

• chr16-69718561-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

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	HGVSp	Effect	#exon/exons	MANE	UniProt
NQO1	NM_000903.3	c.8-27G>C		intron_variant		ENST00000320623.10
NQO1	NM_001025433.2	c.8-27G>C		intron_variant
NQO1	NM_001025434.2	c.8-27G>C		intron_variant
NQO1	NM_001286137.2	c.8-27G>C		intron_variant

Ensembl

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

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

GnomAD3 exomes AF: 0.860 AC: 212189 AN: 246816 Hom.: 91895 AF XY: 0.856 AC XY: 114415 AN XY: 133612

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

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.: 32 AF XY: 0.863 AC XY: 64218 AN XY: 74392

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

Other links and lift over

dbSNP: rs689452; hg19: chr16-69752464;