rs4149360

Variant names:

• chr6-3006573-A-G
• rs4149360
• NM_000904.6:c.7+14A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000904.6(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 NM_000904.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NQO2	NM_000904.6	c.7+14A>G		intron_variant	Intron 2 of 6	ENST00000380455.11	NP_000895.2
NQO2	NM_001290221.2	c.7+14A>G		intron_variant	Intron 5 of 9		NP_001277150.1
NQO2	NM_001318940.2	c.7+14A>G		intron_variant	Intron 2 of 6		NP_001305869.1
NQO2	NM_001290222.2	c.7+14A>G		intron_variant	Intron 2 of 5		NP_001277151.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NQO2	ENST00000380455.11	c.7+14A>G		intron_variant	Intron 2 of 6	1	NM_000904.6	ENSP00000369822.4

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

GnomAD2 exomes AF: 0.187 AC: 39489 AN: 210714 AF XY: 0.187

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 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

African (AFR) AF: 0.0526 AC: 1691 AN: 32152

American (AMR) AF: 0.193 AC: 7684 AN: 39878

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 3510 AN: 25574

East Asian (EAS) AF: 0.100 AC: 3888 AN: 38698

South Asian (SAS) AF: 0.114 AC: 9314 AN: 81364

European-Finnish (FIN) AF: 0.214 AC: 11242 AN: 52490

Middle Eastern (MID) AF: 0.111 AC: 632 AN: 5688

European-Non Finnish (NFE) AF: 0.224 AC: 247238 AN: 1101576

Other (OTH) AF: 0.185 AC: 10969 AN: 59384

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

African (AFR) AF: 0.0551 AC: 2281 AN: 41366

American (AMR) AF: 0.179 AC: 2722 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3468

East Asian (EAS) AF: 0.123 AC: 634 AN: 5150

South Asian (SAS) AF: 0.118 AC: 569 AN: 4812

European-Finnish (FIN) AF: 0.221 AC: 2312 AN: 10446

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14802 AN: 67888

Other (OTH) AF: 0.153 AC: 322 AN: 2102

Alfa AF: 0.193 Hom.: 5381

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
PhyloP100		-0.34
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: rs4149360; hg19: chr6-3006807; COSMIC: COSV57642353;