dbSNP rs1800779: NOS3:c.-51-898G>A (chr7-150992855-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025): 0P and 4B. B1_Strong

The NM_000603.5(NOS3):c.-51-898G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The gene NOS3 is a known oncogene (CancerMine: 2 oncogene citations). The variant allele was found at a cumulative frequency of 0.706 (AC=107,300) in the gnomAD database across 152,026 control chromosomes, including 38,819 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.869. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.71 ( 38819 hom., cov: 31)

Consequence

NOS3
NM_000603.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.118

Publications

113 publications found

Variant links:

Genes affected

NOS3 (HGNC:7876): (nitric oxide synthase 3) Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. Nitric oxide is synthesized from L-arginine by nitric oxide synthases. Variations in this gene are associated with susceptibility to coronary spasm. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]

NOS3 links:

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new If you want to explore the variant's impact on the transcript NM_000603.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 points.

GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.869 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000603.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	NM_000603.5	MANE Select	c.-51-898G>A		intron	N/A	NP_000594.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.-51-898G>A		intron	N/A	ENSP00000297494.3	P29474-1
	NOS3	ENST00000461406.5	TSL:2	c.-149+1555G>A		intron	N/A	ENSP00000417143.1	E7ESA7

Frequencies

GnomAD3 genomes

AF:

0.706

AC:

107185

AN:

151906

Hom.:

38764

Cov.:

show subpopulations

Gnomad AFR

AF:

0.843

Gnomad AMI

AF:

0.715

Gnomad AMR

AF:

0.692

Gnomad ASJ

AF:

0.646

Gnomad EAS

AF:

0.890

Gnomad SAS

AF:

0.776

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.619

Gnomad OTH

AF:

0.664

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.706

AC:

107300

AN:

152026

Hom.:

38819

Cov.:

AF XY:

0.709

AC XY:

52675

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.843

AC:

34956

AN:

41464

American (AMR)

AF:

0.693

AC:

10587

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.646

AC:

2241

AN:

3470

East Asian (EAS)

AF:

0.890

AC:

4596

AN:

5164

South Asian (SAS)

AF:

0.776

AC:

3741

AN:

4820

European-Finnish (FIN)

AF:

0.652

AC:

6894

AN:

10568

Middle Eastern (MID)

AF:

0.633

AC:

186

AN:

294

European-Non Finnish (NFE)

AF:

0.619

AC:

42042

AN:

67946

Other (OTH)

AF:

0.667

AC:

1408

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1544

3087

4631

6174

7718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

824

1648

2472

3296

4120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.649

Hom.:

41836

Bravo

AF:

0.718

Asia WGS

AF:

0.832

AC:

2892

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.892

AC:

109459

AN:

122726

Turkish Variome

AF:

0.670

AC:

1036

AN:

1546

Hom.:

343

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.889

AC:

7966

AN:

8960

Hom.:

3552

ABraOM SABE-WGS-1171

AF:

0.652

AC:

1526

AN:

2342

Hom.:

494

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

8.5

(source)

DANN

Benign

0.79

PhyloP100

0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over