rs4149360

Positions:

• chr6-3006573-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000380455.11(NQO2):​c.7+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,588,476 control chromosomes in the GnomAD database, including 34,947 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 0.16 (2436 hom., cov: 31)
  • Exomes 𝑓: 0.21 (32511 hom.)
• Consequence: NQO2 ENST00000380455.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

Genes affected

NQO2 (HGNC:7856): (N-ribosyldihydronicotinamide:quinone dehydrogenase 2) This gene encodes a member of the thioredoxin family of enzymes. It is a cytosolic and ubiquitously expressed flavoprotein that catalyzes the two-electron reduction of quinone substrates and uses dihydronicotinamide riboside as a reducing coenzyme. Mutations in this gene have been associated with neurodegenerative diseases and several cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NQO2	NM_000904.6	c.7+14A>G		intron_variant		ENST00000380455.11	NP_000895.2
NQO2	NM_001290221.2	c.7+14A>G		intron_variant			NP_001277150.1
NQO2	NM_001290222.2	c.7+14A>G		intron_variant			NP_001277151.1
NQO2	NM_001318940.2	c.7+14A>G		intron_variant			NP_001305869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NQO2	ENST00000380455.11	c.7+14A>G		intron_variant		1	NM_000904.6	ENSP00000369822	P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24340 AN: 151554 Hom.: 2435 Cov.: 31

Gnomad AFR AF: 0.0551

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.154

GnomAD3 exomes AF: 0.187 AC: 39489 AN: 210714 Hom.: 3890 AF XY: 0.187 AC XY: 21227 AN XY: 113694

Gnomad AFR exome AF: 0.0573

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.144

Gnomad EAS exome AF: 0.134

Gnomad SAS exome AF: 0.121

Gnomad FIN exome AF: 0.221

Gnomad NFE exome AF: 0.222

Gnomad OTH exome AF: 0.183

GnomAD4 exome AF: 0.206 AC: 296168 AN: 1436804 Hom.: 32511 Cov.: 32 AF XY: 0.203 AC XY: 145082 AN XY: 713480

Gnomad4 AFR exome AF: 0.0526

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.100

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.161 AC: 24345 AN: 151672 Hom.: 2436 Cov.: 31 AF XY: 0.161 AC XY: 11953 AN XY: 74100

Gnomad4 AFR AF: 0.0551

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.153

Alfa AF: 0.196 Hom.: 4398

Bravo AF: 0.155

Asia WGS AF: 0.118 AC: 409 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.040
DANN	Benign	0.32

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: rs4149360; hg19: chr6-3006807; COSMIC: COSV57642353;