rs2297518

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000625.4(NOS2):c.1823C>T(p.Ser608Leu) variant causes a missense change. The variant allele was found at a frequency of 0.184 in 1,608,552 control chromosomes in the GnomAD database, including 28,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.17 ( 2373 hom., cov: 33)

Exomes 𝑓: 0.18 ( 26033 hom. )

Consequence

NOS2
NM_000625.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 6.41

Variant links:

Genes affected

NOS2 (HGNC:7873): (nitric oxide synthase 2) Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. This gene encodes a nitric oxide synthase which is expressed in liver and is inducible by a combination of lipopolysaccharide and certain cytokines. Three related pseudogenes are located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

NOS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028576553).

BP6

Variant 17-27769571-G-A is Benign according to our data. Variant chr17-27769571-G-A is described in ClinVar as [Benign]. Clinvar id is 2688228.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4 link	c.1823C>T	p.Ser608Leu	missense_variant	Exon 16 of 27	ENST00000313735.11	NP_000616.3	P35228-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11 link	c.1823C>T	p.Ser608Leu	missense_variant	Exon 16 of 27	1	NM_000625.4	ENSP00000327251.6		P35228-1

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26142

AN:

151996

Hom.:

2375

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.458

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.194

Gnomad OTH

AF:

0.197

GnomAD2 exomes

AF:

0.177

AC:

44586

AN:

251380

AF XY:

0.183

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.129

Gnomad ASJ exome

AF:

0.257

Gnomad EAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.181

Gnomad NFE exome

AF:

0.195

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.185

AC:

269171

AN:

1456438

Hom.:

26033

Cov.:

AF XY:

0.186

AC XY:

134655

AN XY:

724896

show subpopulations

Gnomad4 AFR exome

AF:

0.118

AC:

3955

AN:

33392

Gnomad4 AMR exome

AF:

0.133

AC:

5966

AN:

44710

Gnomad4 ASJ exome

AF:

0.253

AC:

6589

AN:

26082

Gnomad4 EAS exome

AF:

0.102

AC:

4056

AN:

39686

Gnomad4 SAS exome

AF:

0.180

AC:

15467

AN:

86112

Gnomad4 FIN exome

AF:

0.179

AC:

9559

AN:

53404

Gnomad4 NFE exome

AF:

0.191

AC:

211002

AN:

1107092

Gnomad4 Remaining exome

AF:

0.187

AC:

11261

AN:

60212

Heterozygous variant carriers

10099

20198

30297

40396

50495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

7230

14460

21690

28920

36150

<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:

0.172

AC:

26144

AN:

152114

Hom.:

2373

Cov.:

AF XY:

0.173

AC XY:

12838

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.121

AC:

0.121295

AN:

0.121295

Gnomad4 AMR

AF:

0.168

AC:

0.167801

AN:

0.167801

Gnomad4 ASJ

AF:

0.256

AC:

0.256484

AN:

0.256484

Gnomad4 EAS

AF:

0.149

AC:

0.149363

AN:

0.149363

Gnomad4 SAS

AF:

0.173

AC:

0.173245

AN:

0.173245

Gnomad4 FIN

AF:

0.188

AC:

0.188221

AN:

0.188221

Gnomad4 NFE

AF:

0.194

AC:

0.193556

AN:

0.193556

Gnomad4 OTH

AF:

0.195

AC:

0.194891

AN:

0.194891

Heterozygous variant carriers

1124

2248

3373

4497

5621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<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:

0.188

Hom.:

13156

Bravo

AF:

0.170

TwinsUK

AF:

0.200

AC:

743

ALSPAC

AF:

0.189

AC:

727

ESP6500AA

AF:

0.113

AC:

500

ESP6500EA

AF:

0.195

AC:

1680

ExAC

AF:

0.178

AC:

21575

Asia WGS

AF:

0.140

AC:

486

AN:

3478

EpiCase

AF:

0.203

EpiControl

AF:

0.197

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 32% of patients studied by a panel of primary immunodeficiencies. Number of patients: 30. Only high quality variants are reported. -

NOS2-related disorder

Benign:1

Nov 04, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;.;.

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

D;D;D

MetaRNN

Benign

0.0029

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.5

L;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.8

D;.;.

REVEL

Benign

0.25

Sift

Benign

0.12

T;.;.

Sift4G

Benign

0.10

T;.;T

Polyphen

0.92

P;.;.

Vest4

0.24

MPC

2.6

ClinPred

0.023

GERP RS

5.3

Varity_R

0.46

gMVP

0.54

Mutation Taster

=88/12

polymorphism (auto)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over