rs34755915

chr16-69718103-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000903.3(NQO1):c.303+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,613,700 control chromosomes in the GnomAD database, including 193 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 0.0089 (12 hom., cov: 32)
  • Exomes 𝑓: 0.013 (181 hom.)
• Consequence: NQO1 NM_000903.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54

Genes affected

NQO1 (HGNC:2874): (NAD(P)H quinone dehydrogenase 1) This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase. This FAD-binding protein forms homodimers and reduces quinones to hydroquinones. This protein's enzymatic activity prevents the one electron reduction of quinones that results in the production of radical species. Mutations in this gene have been associated with tardive dyskinesia (TD), an increased risk of hematotoxicity after exposure to benzene, and susceptibility to various forms of cancer. Altered expression of this protein has been seen in many tumors and is also associated with Alzheimer's disease (AD). Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0133 (19364/1461336) while in subpopulation NFE AF= 0.0161 (17936/1111710). AF 95% confidence interval is 0.0159. There are 181 homozygotes in gnomad4_exome. There are 9466 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NQO1	NM_000903.3	c.303+20G>A		intron_variant		ENST00000320623.10
NQO1	NM_001025433.2	c.303+20G>A		intron_variant
NQO1	NM_001025434.2	c.303+20G>A		intron_variant
NQO1	NM_001286137.2	c.303+20G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NQO1	ENST00000320623.10	c.303+20G>A		intron_variant		1	NM_000903.3	P1

Frequencies

GnomAD3 genomes AF: 0.00895 AC: 1363 AN: 152246 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00268

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00555

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0157

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00879 AC: 2205 AN: 250744 Hom.: 16 AF XY: 0.00922 AC XY: 1250 AN XY: 135550

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.00383

Gnomad ASJ exome AF: 0.00996

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000980

Gnomad FIN exome AF: 0.00555

Gnomad NFE exome AF: 0.0155

Gnomad OTH exome AF: 0.00637

GnomAD4 exome AF: 0.0133 AC: 19364 AN: 1461336 Hom.: 181 Cov.: 30 AF XY: 0.0130 AC XY: 9466 AN XY: 727006

Gnomad4 AFR exome AF: 0.00206

Gnomad4 AMR exome AF: 0.00361

Gnomad4 ASJ exome AF: 0.00900

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00109

Gnomad4 FIN exome AF: 0.00491

Gnomad4 NFE exome AF: 0.0161

Gnomad4 OTH exome AF: 0.00999

GnomAD4 genome AF: 0.00895 AC: 1363 AN: 152364 Hom.: 12 Cov.: 32 AF XY: 0.00821 AC XY: 612 AN XY: 74514

Gnomad4 AFR AF: 0.00267

Gnomad4 AMR AF: 0.00490

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00555

Gnomad4 NFE AF: 0.0157

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.0128 Hom.: 5

Bravo AF: 0.00867

Asia WGS AF: 0.00115 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.0
Dann	Benign	0.37

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: rs34755915; hg19: chr16-69752006;