rs689459

Positions:

• chr16-69726719-G-C

Variant summary

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

The NR_186363.1(NQO1-DT):​n.-8G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 400,226 control chromosomes in the GnomAD database, including 604 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 0.044 (495 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (109 hom.)
• Consequence: NQO1-DT NR_186363.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

Genes affected

NQO1-DT (HGNC:55344): (NQO1 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NQO1-DT	NR_186363.1	n.-8G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NQO1-DT	ENST00000690354.1	n.-49G>C		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0435 AC: 6618 AN: 151992 Hom.: 497 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0317

GnomAD4 exome AF: 0.00577 AC: 1432 AN: 248116 Hom.: 109 Cov.: 2 AF XY: 0.00497 AC XY: 639 AN XY: 128638

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.00707

Gnomad4 ASJ exome AF: 0.000112

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000992

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000301

Gnomad4 OTH exome AF: 0.0144

GnomAD4 genome AF: 0.0435 AC: 6618 AN: 152110 Hom.: 495 Cov.: 32 AF XY: 0.0424 AC XY: 3156 AN XY: 74372

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.0144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0314

Alfa AF: 0.0329 Hom.: 31

Bravo AF: 0.0488

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.67

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: rs689459; hg19: chr16-69760622;