Variant rs3729508 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000625.4(NOS2):c.722+11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 1,611,480 control chromosomes in the GnomAD database, including 307,006 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.67 ( 34483 hom., cov: 32)

Exomes 𝑓: 0.61 ( 272523 hom. )

Consequence

NOS2
NM_000625.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.16

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:

NOS2 (HGNC:):

NOS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 17-27782004-T-C is Benign according to our data. Variant chr17-27782004-T-C is described in ClinVar as [Benign]. Clinvar id is 2687961.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 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.722+11A>G		intron_variant		ENST00000313735.11	NP_000616.3	P35228-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11 linkuse as main transcript	c.722+11A>G		intron_variant		1	NM_000625.4	ENSP00000327251.6		P35228-1

Frequencies

GnomAD3 genomes

AF:

0.667

AC:

101331

AN:

151932

Hom.:

34425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.799

Gnomad AMI

AF:

0.748

Gnomad AMR

AF:

0.688

Gnomad ASJ

AF:

0.650

Gnomad EAS

AF:

0.511

Gnomad SAS

AF:

0.740

Gnomad FIN

AF:

0.602

Gnomad MID

AF:

0.736

Gnomad NFE

AF:

0.598

Gnomad OTH

AF:

0.659

GnomAD3 exomes

AF:

0.640

AC:

160086

AN:

250122

Hom.:

52025

AF XY:

0.640

AC XY:

86463

AN XY:

135134

show subpopulations

Gnomad AFR exome

AF:

0.804

Gnomad AMR exome

AF:

0.713

Gnomad ASJ exome

AF:

0.648

Gnomad EAS exome

AF:

0.525

Gnomad SAS exome

AF:

0.733

Gnomad FIN exome

AF:

0.600

Gnomad NFE exome

AF:

0.595

Gnomad OTH exome

AF:

0.639

GnomAD4 exome

AF:

0.608

AC:

887227

AN:

1459430

Hom.:

272523

Cov.:

AF XY:

0.611

AC XY:

443554

AN XY:

726084

show subpopulations

Gnomad4 AFR exome

AF:

0.812

Gnomad4 AMR exome

AF:

0.709

Gnomad4 ASJ exome

AF:

0.652

Gnomad4 EAS exome

AF:

0.506

Gnomad4 SAS exome

AF:

0.730

Gnomad4 FIN exome

AF:

0.599

Gnomad4 NFE exome

AF:

0.590

Gnomad4 OTH exome

AF:

0.624

GnomAD4 genome

AF:

0.667

AC:

101451

AN:

152050

Hom.:

34483

Cov.:

AF XY:

0.670

AC XY:

49813

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.800

Gnomad4 AMR

AF:

0.689

Gnomad4 ASJ

AF:

0.650

Gnomad4 EAS

AF:

0.510

Gnomad4 SAS

AF:

0.741

Gnomad4 FIN

AF:

0.602

Gnomad4 NFE

AF:

0.598

Gnomad4 OTH

AF:

0.660

Alfa

AF:

0.612

Hom.:

41398

Bravo

AF:

0.677

Asia WGS

AF:

0.629

AC:

2191

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

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 86% of patients studied by a panel of primary immunodeficiencies. Number of patients: 82. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.93

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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