6-2997310-A-C

Variant names:

• chr6-2997310-A-C
• rs9405188
• ENST00000380472.7:c.-86+3257A>C

Variant summary

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

The ENST00000380472.7(NQO2):​c.-86+3257A>C variant causes a intron 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 ENST00000380472.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.816
• Publications: 10 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]

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NQO2-AS1	NR_186364.1	n.1059+1307T>G		intron_variant	Intron 1 of 1
NQO2-AS1	NR_186365.1	n.716+1307T>G		intron_variant	Intron 2 of 2
NQO2-AS1	NR_186366.1	n.663+1703T>G		intron_variant	Intron 1 of 1
NQO2-AS1	NR_186367.1	n.285+2081T>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NQO2	ENST00000380472.7	c.-86+3257A>C		intron_variant	Intron 2 of 5	5		ENSP00000369839.3
NQO2	ENST00000426637.5	c.-86+3257A>C		intron_variant	Intron 3 of 5	5		ENSP00000406951.1
NQO2-AS1	ENST00000429319.1	n.122+1703T>G		intron_variant	Intron 1 of 1	2

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

African (AFR) AF: 0.220 AC: 9133 AN: 41514

American (AMR) AF: 0.200 AC: 3053 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3468

East Asian (EAS) AF: 0.144 AC: 748 AN: 5192

South Asian (SAS) AF: 0.149 AC: 718 AN: 4822

European-Finnish (FIN) AF: 0.196 AC: 2078 AN: 10594

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14714 AN: 67996

Other (OTH) AF: 0.196 AC: 415 AN: 2116

Alfa AF: 0.203 Hom.: 3988

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
PhyloP100		0.82

Splicing

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

Other links and lift over

dbSNP: rs9405188; hg19: chr6-2997544;