Variant chr17-27765605-A-G 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.2358T>C(p.Gly786=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 1,612,444 control chromosomes in the GnomAD database, including 329,856 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.68 ( 35461 hom., cov: 34)

Exomes 𝑓: 0.63 ( 294395 hom. )

Consequence

NOS2
NM_000625.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.751

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=-0.57).

BP6

Variant 17-27765605-A-G is Benign according to our data. Variant chr17-27765605-A-G is described in ClinVar as [Benign]. Clinvar id is 2687957.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.751 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS2	NM_000625.4 linkuse as main transcript	c.2358T>C	p.Gly786=	synonymous_variant	20/27	ENST00000313735.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS2	ENST00000313735.11 linkuse as main transcript	c.2358T>C	p.Gly786=	synonymous_variant	20/27	1	NM_000625.4	P2	P35228-1

Frequencies

GnomAD3 genomes

AF:

0.677

AC:

103029

AN:

152086

Hom.:

35407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.781

Gnomad AMI

AF:

0.763

Gnomad AMR

AF:

0.663

Gnomad ASJ

AF:

0.686

Gnomad EAS

AF:

0.693

Gnomad SAS

AF:

0.833

Gnomad FIN

AF:

0.610

Gnomad MID

AF:

0.801

Gnomad NFE

AF:

0.613

Gnomad OTH

AF:

0.689

GnomAD3 exomes

AF:

0.657

AC:

163615

AN:

248954

Hom.:

54859

AF XY:

0.665

AC XY:

89783

AN XY:

135082

show subpopulations

Gnomad AFR exome

AF:

0.785

Gnomad AMR exome

AF:

0.615

Gnomad ASJ exome

AF:

0.681

Gnomad EAS exome

AF:

0.690

Gnomad SAS exome

AF:

0.832

Gnomad FIN exome

AF:

0.600

Gnomad NFE exome

AF:

0.608

Gnomad OTH exome

AF:

0.654

GnomAD4 exome

AF:

0.631

AC:

921436

AN:

1460240

Hom.:

294395

Cov.:

AF XY:

0.637

AC XY:

462772

AN XY:

726442

show subpopulations

Gnomad4 AFR exome

AF:

0.794

Gnomad4 AMR exome

AF:

0.619

Gnomad4 ASJ exome

AF:

0.685

Gnomad4 EAS exome

AF:

0.730

Gnomad4 SAS exome

AF:

0.828

Gnomad4 FIN exome

AF:

0.596

Gnomad4 NFE exome

AF:

0.606

Gnomad4 OTH exome

AF:

0.655

GnomAD4 genome

AF:

0.678

AC:

103144

AN:

152204

Hom.:

35461

Cov.:

AF XY:

0.681

AC XY:

50679

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.782

Gnomad4 AMR

AF:

0.663

Gnomad4 ASJ

AF:

0.686

Gnomad4 EAS

AF:

0.692

Gnomad4 SAS

AF:

0.834

Gnomad4 FIN

AF:

0.610

Gnomad4 NFE

AF:

0.613

Gnomad4 OTH

AF:

0.691

Alfa

AF:

0.643

Hom.:

13721

Bravo

AF:

0.679

Asia WGS

AF:

0.773

AC:

2691

AN:

3478

EpiCase

AF:

0.618

EpiControl

AF:

0.621

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 87% of patients studied by a panel of primary immunodeficiencies. Number of patients: 83. Only high quality variants are reported. -

NOS2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

-0.57

CADD

Benign

8.8

DANN

Benign

0.57

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