rs689453

Variant names:

• chr16-69718470-C-T
• rs689453
• NM_000903.3:c.72G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_000903.3(NQO1):​c.72G>A​(p.Glu24Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 1,614,098 control chromosomes in the GnomAD database, including 4,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.062 (330 hom., cov: 32)
  • Exomes 𝑓: 0.071 (4083 hom.)
• Consequence: NQO1 NM_000903.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.183
• Publications: 25 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=-0.34).
• BP6: Variant 16-69718470-C-T is Benign according to our data. Variant chr16-69718470-C-T is described in ClinVar as Benign. ClinVar VariationId is 3055562.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.183 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0746 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NQO1	NM_000903.3	MANE Select	c.72G>A	p.Glu24Glu	synonymous	Exon 2 of 6	NP_000894.1
	NQO1	NM_001025433.2		c.72G>A	p.Glu24Glu	synonymous	Exon 2 of 5	NP_001020604.1
	NQO1	NM_001025434.2		c.72G>A	p.Glu24Glu	synonymous	Exon 2 of 5	NP_001020605.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NQO1	ENST00000320623.10	TSL:1 MANE Select	c.72G>A	p.Glu24Glu	synonymous	Exon 2 of 6	ENSP00000319788.5
	NQO1	ENST00000564043.1	TSL:1	c.9G>A	p.Glu3Glu	synonymous	Exon 2 of 6	ENSP00000455020.1
	NQO1	ENST00000379047.7	TSL:1	c.72G>A	p.Glu24Glu	synonymous	Exon 2 of 5	ENSP00000368335.3

Frequencies

GnomAD3 genomes AF: 0.0624 AC: 9497 AN: 152144 Hom.: 327 Cov.: 32

Gnomad AFR AF: 0.0506

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0267

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0763

Gnomad OTH AF: 0.0664

GnomAD2 exomes AF: 0.0584 AC: 14668 AN: 251314 AF XY: 0.0584

Gnomad AFR exome AF: 0.0472

Gnomad AMR exome AF: 0.0369

Gnomad ASJ exome AF: 0.0709

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0712

Gnomad NFE exome AF: 0.0793

Gnomad OTH exome AF: 0.0662

GnomAD4 exome AF: 0.0710 AC: 103772 AN: 1461836 Hom.: 4083 Cov.: 31 AF XY: 0.0695 AC XY: 50559 AN XY: 727210

African (AFR) AF: 0.0518 AC: 1733 AN: 33478

American (AMR) AF: 0.0394 AC: 1763 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0756 AC: 1975 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0305 AC: 2627 AN: 86256

European-Finnish (FIN) AF: 0.0716 AC: 3820 AN: 53380

Middle Eastern (MID) AF: 0.0974 AC: 562 AN: 5768

European-Non Finnish (NFE) AF: 0.0784 AC: 87193 AN: 1112002

Other (OTH) AF: 0.0679 AC: 4099 AN: 60392

GnomAD4 genome AF: 0.0625 AC: 9515 AN: 152262 Hom.: 330 Cov.: 32 AF XY: 0.0609 AC XY: 4532 AN XY: 74436

African (AFR) AF: 0.0510 AC: 2119 AN: 41554

American (AMR) AF: 0.0521 AC: 796 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 262 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.0265 AC: 128 AN: 4822

European-Finnish (FIN) AF: 0.0694 AC: 737 AN: 10612

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0763 AC: 5192 AN: 68016

Other (OTH) AF: 0.0662 AC: 140 AN: 2114

Alfa AF: 0.0725 Hom.: 1070

Bravo AF: 0.0626

Asia WGS AF: 0.0200 AC: 70 AN: 3478

EpiCase AF: 0.0815

EpiControl AF: 0.0808

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NQO1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.6
DANN	Benign	0.55
PhyloP100		-0.18
Mutation Taster		=99/1	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: rs689453; hg19: chr16-69752373; COSMIC: COSV57731156;