Variant rs9282801 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.1859+88G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,117,100 control chromosomes in the GnomAD database, including 62,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.32 ( 7966 hom., cov: 32)

Exomes 𝑓: 0.33 ( 54765 hom. )

Consequence

NOS2
NM_000625.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.343

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 17-27769447-C-A is Benign according to our data. Variant chr17-27769447-C-A is described in ClinVar as [Benign]. Clinvar id is 2688094.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.352 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.1859+88G>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.1859+88G>T		intron_variant		1	NM_000625.4	ENSP00000327251.6		P35228-1

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48699

AN:

151842

Hom.:

7955

Cov.:

show subpopulations

Gnomad AFR

AF:

0.267

Gnomad AMI

AF:

0.618

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.451

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.364

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.361

GnomAD4 exome

AF:

0.331

AC:

319125

AN:

965138

Hom.:

54765

AF XY:

0.335

AC XY:

167419

AN XY:

500476

show subpopulations

Gnomad4 AFR exome

AF:

0.264

Gnomad4 AMR exome

AF:

0.238

Gnomad4 ASJ exome

AF:

0.439

Gnomad4 EAS exome

AF:

0.174

Gnomad4 SAS exome

AF:

0.361

Gnomad4 FIN exome

AF:

0.304

Gnomad4 NFE exome

AF:

0.342

Gnomad4 OTH exome

AF:

0.337

GnomAD4 genome

AF:

0.321

AC:

48749

AN:

151962

Hom.:

7966

Cov.:

AF XY:

0.321

AC XY:

23842

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.267

Gnomad4 AMR

AF:

0.288

Gnomad4 ASJ

AF:

0.451

Gnomad4 EAS

AF:

0.203

Gnomad4 SAS

AF:

0.366

Gnomad4 FIN

AF:

0.305

Gnomad4 NFE

AF:

0.356

Gnomad4 OTH

AF:

0.365

Alfa

AF:

0.342

Hom.:

2200

Bravo

AF:

0.315

Asia WGS

AF:

0.297

AC:

1034

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 55% of patients studied by a panel of primary immunodeficiencies. Number of patients: 52. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.1

DANN

Benign

0.77

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