chr7-150998638-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000603.5(NOS3):c.774T>C(p.Asp258Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 1,607,270 control chromosomes in the GnomAD database, including 411,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 44840 hom., cov: 33)

Exomes 𝑓: 0.71 ( 366949 hom. )

Consequence

NOS3
NM_000603.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.51

Publications

67 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

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 7-150998638-T-C is Benign according to our data. Variant chr7-150998638-T-C is described in ClinVar as Benign. ClinVar VariationId is 403248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS3	NM_000603.5 link	c.774T>C	p.Asp258Asp	synonymous_variant	Exon 7 of 27	ENST00000297494.8	NP_000594.2	P29474-1
NOS3	NM_001160111.1 link	c.774T>C	p.Asp258Asp	synonymous_variant	Exon 6 of 14		NP_001153583.1	P29474-2
NOS3	NM_001160110.1 link	c.774T>C	p.Asp258Asp	synonymous_variant	Exon 6 of 14		NP_001153582.1	P29474-3
NOS3	NM_001160109.2 link	c.774T>C	p.Asp258Asp	synonymous_variant	Exon 6 of 14		NP_001153581.1	P29474A0S0A6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOS3	ENST00000297494.8 link	c.774T>C	p.Asp258Asp	synonymous_variant	Exon 7 of 27	1	NM_000603.5	ENSP00000297494.3	P29474-1
NOS3	ENST00000484524.5 link	c.774T>C	p.Asp258Asp	synonymous_variant	Exon 6 of 14	1		ENSP00000420215.1	P29474-2
NOS3	ENST00000467517.1 link	c.774T>C	p.Asp258Asp	synonymous_variant	Exon 6 of 14	1		ENSP00000420551.1	P29474-3
NOS3	ENST00000461406.5 link	c.156T>C	p.Asp52Asp	synonymous_variant	Exon 4 of 24	2		ENSP00000417143.1	E7ESA7

Frequencies

GnomAD3 genomes

AF:

0.761

AC:

115782

AN:

152070

Hom.:

44777

Cov.:

show subpopulations

Gnomad AFR

AF:

0.883

Gnomad AMI

AF:

0.755

Gnomad AMR

AF:

0.751

Gnomad ASJ

AF:

0.812

Gnomad EAS

AF:

0.819

Gnomad SAS

AF:

0.852

Gnomad FIN

AF:

0.720

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.683

Gnomad OTH

AF:

0.749

GnomAD2 exomes

AF:

0.759

AC:

177937

AN:

234452

AF XY:

0.756

show subpopulations

Gnomad AFR exome

AF:

0.889

Gnomad AMR exome

AF:

0.821

Gnomad ASJ exome

AF:

0.798

Gnomad EAS exome

AF:

0.819

Gnomad FIN exome

AF:

0.719

Gnomad NFE exome

AF:

0.690

Gnomad OTH exome

AF:

0.730

GnomAD4 exome

AF:

0.707

AC:

1028749

AN:

1455082

Hom.:

366949

Cov.:

AF XY:

0.711

AC XY:

514631

AN XY:

723366

show subpopulations

African (AFR)

AF:

0.889

AC:

29754

AN:

33460

American (AMR)

AF:

0.814

AC:

35796

AN:

43956

Ashkenazi Jewish (ASJ)

AF:

0.798

AC:

20724

AN:

25962

East Asian (EAS)

AF:

0.852

AC:

33661

AN:

39524

South Asian (SAS)

AF:

0.853

AC:

72856

AN:

85402

European-Finnish (FIN)

AF:

0.726

AC:

36962

AN:

50916

Middle Eastern (MID)

AF:

0.766

AC:

4405

AN:

5748

European-Non Finnish (NFE)

AF:

0.676

AC:

750686

AN:

1110020

Other (OTH)

AF:

0.731

AC:

43905

AN:

60094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

18556

37111

55667

74222

92778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19452

38904

58356

77808

97260

<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:

0.762

AC:

115904

AN:

152188

Hom.:

44840

Cov.:

AF XY:

0.764

AC XY:

56812

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.883

AC:

36684

AN:

41562

American (AMR)

AF:

0.751

AC:

11482

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.812

AC:

2820

AN:

3472

East Asian (EAS)

AF:

0.820

AC:

4213

AN:

5138

South Asian (SAS)

AF:

0.853

AC:

4117

AN:

4828

European-Finnish (FIN)

AF:

0.720

AC:

7621

AN:

10590

Middle Eastern (MID)

AF:

0.765

AC:

225

AN:

294

European-Non Finnish (NFE)

AF:

0.683

AC:

46468

AN:

67998

Other (OTH)

AF:

0.752

AC:

1587

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1417

2833

4250

5666

7083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.733

Hom.:

34479

Bravo

AF:

0.770

Asia WGS

AF:

0.850

AC:

2953

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.58

(source)

DANN

Benign

0.37

PhyloP100

-1.5

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over