chr16-69725317-A-G

Variant names:

• chr16-69725317-A-G
• rs2917669
• NM_000903.3:c.7+1116T>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.7+1116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 152,202 control chromosomes in the GnomAD database, including 55,731 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 0.85 (55731 hom., cov: 33)
• Consequence: NQO1 NM_000903.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114
• Publications: 10 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.897 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.7+1116T>C		intron	N/A	NP_000894.1
	NQO1	NM_001025433.2		c.7+1116T>C		intron	N/A	NP_001020604.1
	NQO1	NM_001025434.2		c.7+1116T>C		intron	N/A	NP_001020605.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NQO1	ENST00000320623.10	TSL:1 MANE Select	c.7+1116T>C		intron	N/A	ENSP00000319788.5
	NQO1	ENST00000564043.1	TSL:1	c.-57+1184T>C		intron	N/A	ENSP00000455020.1
	NQO1	ENST00000379047.7	TSL:1	c.7+1116T>C		intron	N/A	ENSP00000368335.3

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129924 AN: 152084 Hom.: 55694 Cov.: 33

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.847

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.856

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.854 AC: 130014 AN: 152202 Hom.: 55731 Cov.: 33 AF XY: 0.852 AC XY: 63388 AN XY: 74422

African (AFR) AF: 0.825 AC: 34243 AN: 41512

American (AMR) AF: 0.909 AC: 13903 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2952 AN: 3470

East Asian (EAS) AF: 0.639 AC: 3311 AN: 5182

South Asian (SAS) AF: 0.826 AC: 3983 AN: 4824

European-Finnish (FIN) AF: 0.854 AC: 9061 AN: 10606

Middle Eastern (MID) AF: 0.836 AC: 244 AN: 292

European-Non Finnish (NFE) AF: 0.878 AC: 59715 AN: 68012

Other (OTH) AF: 0.855 AC: 1799 AN: 2104

Alfa AF: 0.873 Hom.: 74139

Bravo AF: 0.858

Asia WGS AF: 0.767 AC: 2671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.39
PhyloP100		-0.11
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: rs2917669; hg19: chr16-69759220;