rs1437135

Positions:

• chr16-69723925-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.7+2508T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,014 control chromosomes in the GnomAD database, including 4,578 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 0.24 (4578 hom., cov: 31)
• Consequence: NQO1 NM_000903.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NQO1	NM_000903.3	c.7+2508T>C		intron_variant		ENST00000320623.10	NP_000894.1
NQO1	NM_001025433.2	c.7+2508T>C		intron_variant			NP_001020604.1
NQO1	NM_001025434.2	c.7+2508T>C		intron_variant			NP_001020605.1
NQO1	NM_001286137.2	c.7+2508T>C		intron_variant			NP_001273066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NQO1	ENST00000320623.10	c.7+2508T>C		intron_variant		1	NM_000903.3	ENSP00000319788	P1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35801 AN: 151896 Hom.: 4571 Cov.: 31

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.236 AC: 35835 AN: 152014 Hom.: 4578 Cov.: 31 AF XY: 0.241 AC XY: 17870 AN XY: 74280

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.246

Alfa AF: 0.204 Hom.: 6862

Bravo AF: 0.249

Asia WGS AF: 0.331 AC: 1148 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1437135; hg19: chr16-69757828;