16-69714966-G-T

Variant names:

• chr16-69714966-G-T
• rs1131341
• NM_000903.3:c.415C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_000903.3(NQO1):​c.415C>A​(p.Arg139Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NQO1 NM_000903.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.001127
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.40
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 16-69714966-G-T is Benign according to our data. Variant chr16-69714966-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1738323.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.4 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NQO1	NM_000903.3	MANE Select	c.415C>A	p.Arg139Arg	splice_region synonymous	Exon 4 of 6	NP_000894.1	P15559-1
	NQO1	NM_001025433.2		c.415C>A	p.Arg139Arg	splice_region synonymous	Exon 4 of 5	NP_001020604.1	P15559-2
	NQO1	NM_001025434.2		c.304-1837C>A		intron	N/A	NP_001020605.1	P15559-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NQO1	ENST00000320623.10	TSL:1 MANE Select	c.415C>A	p.Arg139Arg	splice_region synonymous	Exon 4 of 6	ENSP00000319788.5	P15559-1
	NQO1	ENST00000564043.1	TSL:1	c.352C>A	p.Arg118Arg	splice_region synonymous	Exon 4 of 6	ENSP00000455020.1	H3BNV2
	NQO1	ENST00000379047.7	TSL:1	c.415C>A	p.Arg139Arg	splice_region synonymous	Exon 4 of 5	ENSP00000368335.3	P15559-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	9.0
DANN	Benign	0.74
PhyloP100		2.4

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0011
dbscSNV1_RF	Benign	0.072
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: rs1131341; hg19: chr16-69748869;