rs1007311

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000603.5(NOS3):c.817-26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 1,595,936 control chromosomes in the GnomAD database, including 158,234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.46 ( 16531 hom., cov: 31)

Exomes 𝑓: 0.44 ( 141703 hom. )

Consequence

NOS3
NM_000603.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.51

Publications

22 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 -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 7-150998920-A-G is Benign according to our data. Variant chr7-150998920-A-G is described in ClinVar as Benign. ClinVar VariationId is 1256933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NOS3	NM_000603.5	MANE Select	c.817-26A>G	intron	N/A	NP_000594.2
NOS3	NM_001160111.1		c.817-26A>G	intron	N/A	NP_001153583.1	P29474-2
NOS3	NM_001160110.1		c.817-26A>G	intron	N/A	NP_001153582.1	P29474-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NOS3	ENST00000297494.8	TSL:1 MANE Select	c.817-26A>G	intron	N/A	ENSP00000297494.3	P29474-1
NOS3	ENST00000484524.5	TSL:1	c.817-26A>G	intron	N/A	ENSP00000420215.1	P29474-2
NOS3	ENST00000467517.1	TSL:1	c.817-26A>G	intron	N/A	ENSP00000420551.1	P29474-3

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69590

AN:

151714

Hom.:

16515

Cov.:

show subpopulations

Gnomad AFR

AF:

0.560

Gnomad AMI

AF:

0.572

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.503

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.432

Gnomad OTH

AF:

0.456

GnomAD2 exomes

AF:

0.431

AC:

101194

AN:

234618

AF XY:

0.438

show subpopulations

Gnomad AFR exome

AF:

0.564

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.559

Gnomad EAS exome

AF:

0.521

Gnomad FIN exome

AF:

0.368

Gnomad NFE exome

AF:

0.436

Gnomad OTH exome

AF:

0.428

GnomAD4 exome

AF:

0.440

AC:

634701

AN:

1444106

Hom.:

141703

Cov.:

AF XY:

0.442

AC XY:

317001

AN XY:

717558

show subpopulations

African (AFR)

AF:

0.564

AC:

18376

AN:

32604

American (AMR)

AF:

0.254

AC:

10495

AN:

41262

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

14277

AN:

25318

East Asian (EAS)

AF:

0.490

AC:

19344

AN:

39482

South Asian (SAS)

AF:

0.494

AC:

41929

AN:

84816

European-Finnish (FIN)

AF:

0.380

AC:

19664

AN:

51760

Middle Eastern (MID)

AF:

0.500

AC:

2590

AN:

5180

European-Non Finnish (NFE)

AF:

0.435

AC:

480850

AN:

1104196

Other (OTH)

AF:

0.457

AC:

27176

AN:

59488

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

17247

34494

51742

68989

86236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14800

29600

44400

59200

74000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.459

AC:

69631

AN:

151830

Hom.:

16531

Cov.:

AF XY:

0.454

AC XY:

33670

AN XY:

74184

show subpopulations

African (AFR)

AF:

0.559

AC:

23137

AN:

41378

American (AMR)

AF:

0.317

AC:

4840

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.569

AC:

1975

AN:

3468

East Asian (EAS)

AF:

0.503

AC:

2590

AN:

5148

South Asian (SAS)

AF:

0.479

AC:

2301

AN:

4802

European-Finnish (FIN)

AF:

0.362

AC:

3821

AN:

10566

Middle Eastern (MID)

AF:

0.510

AC:

149

AN:

292

European-Non Finnish (NFE)

AF:

0.432

AC:

29328

AN:

67878

Other (OTH)

AF:

0.460

AC:

971

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1917

3833

5750

7666

9583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.462

Hom.:

3095

Bravo

AF:

0.458

Asia WGS

AF:

0.493

AC:

1714

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.047

(source)

DANN

Benign

0.36

PhyloP100

-2.5

BranchPoint Hunter

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over