rs1437135

Variant names:

• chr16-69723925-A-G
• rs1437135
• NM_000903.3:c.7+2508T>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+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
• Publications: 21 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=-0.81).
• 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 rank	MANE	Protein	UniProt
NQO1	NM_000903.3	c.7+2508T>C		intron_variant	Intron 1 of 5	ENST00000320623.10	NP_000894.1
NQO1	NM_001025433.2	c.7+2508T>C		intron_variant	Intron 1 of 4		NP_001020604.1
NQO1	NM_001025434.2	c.7+2508T>C		intron_variant	Intron 1 of 4		NP_001020605.1
NQO1	NM_001286137.2	c.7+2508T>C		intron_variant	Intron 1 of 3		NP_001273066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NQO1	ENST00000320623.10	c.7+2508T>C		intron_variant	Intron 1 of 5	1	NM_000903.3	ENSP00000319788.5

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

African (AFR) AF: 0.252 AC: 10448 AN: 41458

American (AMR) AF: 0.336 AC: 5127 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 618 AN: 3466

East Asian (EAS) AF: 0.448 AC: 2316 AN: 5164

South Asian (SAS) AF: 0.334 AC: 1609 AN: 4818

European-Finnish (FIN) AF: 0.189 AC: 2002 AN: 10578

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12940 AN: 67974

Other (OTH) AF: 0.246 AC: 519 AN: 2110

Alfa AF: 0.207 Hom.: 10595

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
PhyloP100		-0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1437135; hg19: chr16-69757828;