Variant rs3729966 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.1476+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,366,358 control chromosomes in the GnomAD database, including 33,411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.20 ( 3124 hom., cov: 32)

Exomes 𝑓: 0.22 ( 30287 hom. )

Consequence

NOS2
NM_000625.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.961

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 17-27774211-G-A is Benign according to our data. Variant chr17-27774211-G-A is described in ClinVar as [Benign]. Clinvar id is 2688145.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 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.1476+46C>T		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.1476+46C>T		intron_variant		1	NM_000625.4	ENSP00000327251.6		P35228-1

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

29929

AN:

151696

Hom.:

3125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.291

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.213

GnomAD3 exomes

AF:

0.214

AC:

26684

AN:

124684

Hom.:

2957

AF XY:

0.214

AC XY:

14186

AN XY:

66340

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.297

Gnomad ASJ exome

AF:

0.173

Gnomad EAS exome

AF:

0.293

Gnomad SAS exome

AF:

0.260

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.203

GnomAD4 exome

AF:

0.221

AC:

268520

AN:

1214544

Hom.:

30287

Cov.:

AF XY:

0.222

AC XY:

131494

AN XY:

593072

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.294

Gnomad4 ASJ exome

AF:

0.177

Gnomad4 EAS exome

AF:

0.354

Gnomad4 SAS exome

AF:

0.264

Gnomad4 FIN exome

AF:

0.184

Gnomad4 NFE exome

AF:

0.218

Gnomad4 OTH exome

AF:

0.222

GnomAD4 genome

AF:

0.197

AC:

29938

AN:

151814

Hom.:

3124

Cov.:

AF XY:

0.198

AC XY:

14684

AN XY:

74182

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.274

Gnomad4 ASJ

AF:

0.169

Gnomad4 EAS

AF:

0.291

Gnomad4 SAS

AF:

0.264

Gnomad4 FIN

AF:

0.178

Gnomad4 NFE

AF:

0.216

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.193

Hom.:

561

Bravo

AF:

0.198

Asia WGS

AF:

0.255

AC:

890

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 45% of patients studied by a panel of primary immunodeficiencies. Number of patients: 43. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.24

DANN

Benign

0.67

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