rs9405188

chr6-2997310-A-C

Variant summary

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

The ENST00000660868.1(NQO2-AS1):n.592+1703T>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,180 control chromosomes in the GnomAD database, including 3,302 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 0.21 (3302 hom., cov: 32)
• Consequence: NQO2-AS1 ENST00000660868.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.816

Genes affected

NQO2-AS1 (HGNC:40407): (NQO2 antisense RNA 1)

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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NQO2-AS1	ENST00000660868.1	n.592+1703T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31464 AN: 152062 Hom.: 3298 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.207 AC: 31502 AN: 152180 Hom.: 3302 Cov.: 32 AF XY: 0.205 AC XY: 15276 AN XY: 74392

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.196

Alfa AF: 0.200 Hom.: 2903

Bravo AF: 0.209

Asia WGS AF: 0.151 AC: 523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	11
Dann	Benign	0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9405188; hg19: chr6-2997544;