16-69709857-A-G

Position:

• chr16-69709857-A-G

Variant summary

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

The NM_000903.3(NQO1):​c.*1119T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 398,488 control chromosomes in the GnomAD database, including 144,332 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 0.86 (56264 hom., cov: 33)
  • Exomes 𝑓: 0.84 (88068 hom.)
• Consequence: NQO1 NM_000903.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NQO1	NM_000903.3	c.*1119T>C		3_prime_UTR_variant	6/6	ENST00000320623.10
NQO1	NM_001025433.2	c.*1119T>C		3_prime_UTR_variant	5/5
NQO1	NM_001025434.2	c.*1119T>C		3_prime_UTR_variant	5/5
NQO1	NM_001286137.2	c.*1119T>C		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NQO1	ENST00000320623.10	c.*1119T>C		3_prime_UTR_variant	6/6	1	NM_000903.3	P1
NQO1	ENST00000379047.7	c.*1119T>C		3_prime_UTR_variant	5/5	1
NQO1	ENST00000561500.5	c.612+1218T>C		intron_variant		3
	ENST00000562696.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130523 AN: 152108 Hom.: 56222 Cov.: 33

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.863

GnomAD4 exome AF: 0.843 AC: 207644 AN: 246262 Hom.: 88068 Cov.: 0 AF XY: 0.842 AC XY: 105117 AN XY: 124776

Gnomad4 AFR exome AF: 0.847

Gnomad4 AMR exome AF: 0.931

Gnomad4 ASJ exome AF: 0.846

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.837

Gnomad4 FIN exome AF: 0.846

Gnomad4 NFE exome AF: 0.863

Gnomad4 OTH exome AF: 0.852

GnomAD4 genome AF: 0.858 AC: 130618 AN: 152226 Hom.: 56264 Cov.: 33 AF XY: 0.856 AC XY: 63699 AN XY: 74424

Gnomad4 AFR AF: 0.860

Gnomad4 AMR AF: 0.914

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.838

Gnomad4 FIN AF: 0.839

Gnomad4 NFE AF: 0.866

Gnomad4 OTH AF: 0.862

Alfa AF: 0.862 Hom.: 115092

Bravo AF: 0.864

Asia WGS AF: 0.775 AC: 2698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.64

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: rs10517; hg19: chr16-69743760;