dbSNP rs1800779: NOS3:c.-51-898G>A (chr7-150992855-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019): 0P and 12B. BA1BP4_Strong

The NM_000603.5(NOS3):c.-51-898G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.8685 — exceeds 5%% threshold (BA1 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 ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over