Genetic Variant NM_000603.5:c.-51-762C>T (chr7-150992991-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000603.5(NOS3):c.-51-762C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,046 control chromosomes in the GnomAD database, including 38,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (★).

Frequency

Genomes: 𝑓 0.70 ( 38247 hom., cov: 31)

Consequence

NOS3
NM_000603.5 intron

Scores

Clinical Significance

protective criteria provided, single submitter B:1

Conservation

PhyloP100: -1.24

Publications

1110 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:

Genome browser will be placed here

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.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000603.5. 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
	NOS3	NM_000603.5	MANE Select	c.-51-762C>T		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.-51-762C>T		intron	N/A	ENSP00000297494.3	P29474-1
	NOS3	ENST00000461406.5	TSL:2	c.-149+1691C>T		intron	N/A	ENSP00000417143.1	E7ESA7

Frequencies

GnomAD3 genomes

AF:

0.700

AC:

106375

AN:

151928

Hom.:

38192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.841

Gnomad AMI

AF:

0.716

Gnomad AMR

AF:

0.688

Gnomad ASJ

AF:

0.645

Gnomad EAS

AF:

0.890

Gnomad SAS

AF:

0.771

Gnomad FIN

AF:

0.648

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.610

Gnomad OTH

AF:

0.659

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

GnomAD4 genome

AF:

0.700

AC:

106489

AN:

152046

Hom.:

38247

Cov.:

AF XY:

0.704

AC XY:

52330

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.841

AC:

34896

AN:

41488

American (AMR)

AF:

0.688

AC:

10518

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.645

AC:

2239

AN:

3470

East Asian (EAS)

AF:

0.890

AC:

4571

AN:

5138

South Asian (SAS)

AF:

0.771

AC:

3717

AN:

4820

European-Finnish (FIN)

AF:

0.648

AC:

6864

AN:

10588

Middle Eastern (MID)

AF:

0.629

AC:

185

AN:

294

European-Non Finnish (NFE)

AF:

0.610

AC:

41453

AN:

67948

Other (OTH)

AF:

0.662

AC:

1396

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1558

3117

4675

6234

7792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

822

1644

2466

3288

4110

<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:

0.638

Hom.:

48710

Bravo

AF:

0.712

Asia WGS

AF:

0.828

AC:

2879

AN:

3478

ClinVar

ClinVar submissions

Significance:protective

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Metabolic syndrome, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.0

(source)

DANN

Benign

0.48

PhyloP100

-1.2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over