Variant rs1137933 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_000625.4(NOS2):c.1155C>T(p.Asp385=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,606,554 control chromosomes in the GnomAD database, including 38,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.21 ( 3380 hom., cov: 31)

Exomes 𝑓: 0.22 ( 34832 hom. )

Consequence

NOS2
NM_000625.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.631

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 made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 17-27778906-G-A is Benign according to our data. Variant chr17-27778906-G-A is described in ClinVar as [Benign]. Clinvar id is 2688251.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.631 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS2	NM_000625.4 linkuse as main transcript	c.1155C>T	p.Asp385=	synonymous_variant	10/27	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11 linkuse as main transcript	c.1155C>T	p.Asp385=	synonymous_variant	10/27	1	NM_000625.4	ENSP00000327251	P2	P35228-1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31426

AN:

151852

Hom.:

3380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.227

GnomAD3 exomes

AF:

0.205

AC:

50930

AN:

248726

Hom.:

5521

AF XY:

0.209

AC XY:

28148

AN XY:

134414

show subpopulations

Gnomad AFR exome

AF:

0.179

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.168

Gnomad SAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.210

Gnomad NFE exome

AF:

0.228

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

AF:

0.216

AC:

314117

AN:

1454584

Hom.:

34832

Cov.:

AF XY:

0.216

AC XY:

156003

AN XY:

722268

show subpopulations

Gnomad4 AFR exome

AF:

0.179

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.272

Gnomad4 EAS exome

AF:

0.117

Gnomad4 SAS exome

AF:

0.192

Gnomad4 FIN exome

AF:

0.208

Gnomad4 NFE exome

AF:

0.224

Gnomad4 OTH exome

AF:

0.212

GnomAD4 genome

AF:

0.207

AC:

31432

AN:

151970

Hom.:

3380

Cov.:

AF XY:

0.207

AC XY:

15353

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.179

Gnomad4 AMR

AF:

0.189

Gnomad4 ASJ

AF:

0.273

Gnomad4 EAS

AF:

0.166

Gnomad4 SAS

AF:

0.188

Gnomad4 FIN

AF:

0.216

Gnomad4 NFE

AF:

0.224

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.197

Hom.:

1597

Bravo

AF:

0.206

Asia WGS

AF:

0.152

AC:

527

AN:

3478

EpiCase

AF:

0.231

EpiControl

AF:

0.225

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 29% of patients studied by a panel of primary immunodeficiencies. Number of patients: 28. Only high quality variants are reported. -

NOS2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 22, 2019

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

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.9

DANN

Benign

0.35

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