NM_000903.3:c.303+20G>A

Variant names:

• chr16-69718103-C-T
• rs34755915
• NM_000903.3:c.303+20G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 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 GnomAdExome4. There are 9466 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000903.3. 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
	NQO1	NM_000903.3	MANE Select	c.303+20G>A		intron	N/A	NP_000894.1
	NQO1	NM_001025433.2		c.303+20G>A		intron	N/A	NP_001020604.1
	NQO1	NM_001025434.2		c.303+20G>A		intron	N/A	NP_001020605.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NQO1	ENST00000320623.10	TSL:1 MANE Select	c.303+20G>A		intron	N/A	ENSP00000319788.5
	NQO1	ENST00000564043.1	TSL:1	c.240+20G>A		intron	N/A	ENSP00000455020.1
	NQO1	ENST00000379047.7	TSL:1	c.303+20G>A		intron	N/A	ENSP00000368335.3

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

GnomAD2 exomes AF: 0.00879 AC: 2205 AN: 250744 AF XY: 0.00922

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 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

African (AFR) AF: 0.00206 AC: 69 AN: 33456

American (AMR) AF: 0.00361 AC: 161 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00900 AC: 235 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00109 AC: 94 AN: 86224

European-Finnish (FIN) AF: 0.00491 AC: 262 AN: 53400

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5762

European-Non Finnish (NFE) AF: 0.0161 AC: 17936 AN: 1111710

Other (OTH) AF: 0.00999 AC: 603 AN: 60366

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

African (AFR) AF: 0.00267 AC: 111 AN: 41586

American (AMR) AF: 0.00490 AC: 75 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00950 AC: 33 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00555 AC: 59 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0157 AC: 1071 AN: 68038

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.0
DANN	Benign	0.37
PhyloP100		2.5
Mutation Taster		=100/0	polymorphism

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: rs34755915; hg19: chr16-69752006;