16-69709857-A-G

Variant names:

• chr16-69709857-A-G
• rs10517
• NM_000903.3:c.*1119T>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.*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
• Publications: 35 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]

NQO1-AS1 (HGNC:58115):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000903.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NQO1	NM_000903.3	MANE Select	c.*1119T>C		3_prime_UTR	Exon 6 of 6	NP_000894.1	P15559-1
	NQO1	NM_001025433.2		c.*1119T>C		3_prime_UTR	Exon 5 of 5	NP_001020604.1	P15559-2
	NQO1	NM_001025434.2		c.*1119T>C		3_prime_UTR	Exon 5 of 5	NP_001020605.1	P15559-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NQO1	ENST00000320623.10	TSL:1 MANE Select	c.*1119T>C		3_prime_UTR	Exon 6 of 6	ENSP00000319788.5	P15559-1
	NQO1	ENST00000379047.7	TSL:1	c.*1119T>C		3_prime_UTR	Exon 5 of 5	ENSP00000368335.3	P15559-2
	NQO1	ENST00000561500.5	TSL:3	c.612+1218T>C		intron	N/A	ENSP00000456282.1	H3BRK3

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

African (AFR) AF: 0.847 AC: 6085 AN: 7180

American (AMR) AF: 0.931 AC: 6920 AN: 7432

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 7812 AN: 9238

East Asian (EAS) AF: 0.667 AC: 15255 AN: 22882

South Asian (SAS) AF: 0.837 AC: 2537 AN: 3032

European-Finnish (FIN) AF: 0.846 AC: 17617 AN: 20816

Middle Eastern (MID) AF: 0.843 AC: 1091 AN: 1294

European-Non Finnish (NFE) AF: 0.863 AC: 136382 AN: 158022

Other (OTH) AF: 0.852 AC: 13945 AN: 16366

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

African (AFR) AF: 0.860 AC: 35704 AN: 41526

American (AMR) AF: 0.914 AC: 13970 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2946 AN: 3470

East Asian (EAS) AF: 0.636 AC: 3296 AN: 5182

South Asian (SAS) AF: 0.838 AC: 4040 AN: 4822

European-Finnish (FIN) AF: 0.839 AC: 8888 AN: 10588

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.866 AC: 58903 AN: 68028

Other (OTH) AF: 0.862 AC: 1820 AN: 2112

Alfa AF: 0.862 Hom.: 246567

Bravo AF: 0.864

Asia WGS AF: 0.775 AC: 2698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.64
PhyloP100		-0.43
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: rs10517; hg19: chr16-69743760;