NM_000904.6:c.-86+1919T>C

Variant names:

• chr6-3002004-T-C
• rs4149352
• NM_000904.6:c.-86+1919T>C

Variant summary

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

The NM_000904.6(NQO2):​c.-86+1919T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 153,300 control chromosomes in the GnomAD database, including 46,878 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 0.78 (46501 hom., cov: 31)
  • Exomes 𝑓: 0.80 (377 hom.)
• Consequence: NQO2 NM_000904.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 12 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000904.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NQO2	NM_000904.6	MANE Select	c.-86+1919T>C		intron	N/A	NP_000895.2
	NQO2	NM_001290221.2		c.-600-46T>C		intron	N/A	NP_001277150.1
	NQO2	NM_001318940.2		c.-86+1637T>C		intron	N/A	NP_001305869.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NQO2	ENST00000380455.11	TSL:1 MANE Select	c.-86+1919T>C		intron	N/A	ENSP00000369822.4
	NQO2	ENST00000338130.7	TSL:2	c.-600-46T>C		intron	N/A	ENSP00000337773.2
	NQO2	ENST00000380430.6	TSL:5	c.-86+1637T>C		intron	N/A	ENSP00000369795.1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118645 AN: 151994 Hom.: 46449 Cov.: 31

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.750

GnomAD4 exome AF: 0.798 AC: 948 AN: 1188 Hom.: 377 Cov.: 0 AF XY: 0.813 AC XY: 520 AN XY: 640

African (AFR) AF: 0.714 AC: 10 AN: 14

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 4 AN: 8

East Asian (EAS) AF: 0.500 AC: 2 AN: 4

South Asian (SAS) AF: 0.650 AC: 13 AN: 20

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.803 AC: 886 AN: 1104

Other (OTH) AF: 0.889 AC: 32 AN: 36

GnomAD4 genome AF: 0.781 AC: 118757 AN: 152112 Hom.: 46501 Cov.: 31 AF XY: 0.784 AC XY: 58269 AN XY: 74358

African (AFR) AF: 0.825 AC: 34238 AN: 41482

American (AMR) AF: 0.745 AC: 11387 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2307 AN: 3472

East Asian (EAS) AF: 0.668 AC: 3448 AN: 5164

South Asian (SAS) AF: 0.729 AC: 3515 AN: 4820

European-Finnish (FIN) AF: 0.866 AC: 9173 AN: 10598

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.767 AC: 52153 AN: 67972

Other (OTH) AF: 0.751 AC: 1584 AN: 2110

Alfa AF: 0.762 Hom.: 166110

Bravo AF: 0.774

Asia WGS AF: 0.692 AC: 2405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.53
PhyloP100		-1.9
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: rs4149352; hg19: chr6-3002238;