Variant chr17-27781014-T-C 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.864+22A>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 1,608,076 control chromosomes in the GnomAD database, including 306,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.67 ( 34653 hom., cov: 34)

Exomes 𝑓: 0.61 ( 271707 hom. )

Consequence

NOS2
NM_000625.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.531

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-27781014-T-C is Benign according to our data. Variant chr17-27781014-T-C is described in ClinVar as [Benign]. Clinvar id is 2687960.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 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.864+22A>G		intron_variant		ENST00000313735.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS2	ENST00000313735.11 linkuse as main transcript	c.864+22A>G		intron_variant		1	NM_000625.4	P2	P35228-1

Frequencies

GnomAD3 genomes

AF:

0.668

AC:

101629

AN:

152060

Hom.:

34595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.803

Gnomad AMI

AF:

0.747

Gnomad AMR

AF:

0.689

Gnomad ASJ

AF:

0.651

Gnomad EAS

AF:

0.527

Gnomad SAS

AF:

0.739

Gnomad FIN

AF:

0.603

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.597

Gnomad OTH

AF:

0.656

GnomAD3 exomes

AF:

0.641

AC:

158540

AN:

247328

Hom.:

51682

AF XY:

0.641

AC XY:

85755

AN XY:

133834

show subpopulations

Gnomad AFR exome

AF:

0.807

Gnomad AMR exome

AF:

0.713

Gnomad ASJ exome

AF:

0.648

Gnomad EAS exome

AF:

0.541

Gnomad SAS exome

AF:

0.733

Gnomad FIN exome

AF:

0.600

Gnomad NFE exome

AF:

0.594

Gnomad OTH exome

AF:

0.637

GnomAD4 exome

AF:

0.608

AC:

884905

AN:

1455898

Hom.:

271707

Cov.:

AF XY:

0.611

AC XY:

441875

AN XY:

723412

show subpopulations

Gnomad4 AFR exome

AF:

0.817

Gnomad4 AMR exome

AF:

0.710

Gnomad4 ASJ exome

AF:

0.651

Gnomad4 EAS exome

AF:

0.523

Gnomad4 SAS exome

AF:

0.730

Gnomad4 FIN exome

AF:

0.599

Gnomad4 NFE exome

AF:

0.589

Gnomad4 OTH exome

AF:

0.623

GnomAD4 genome

AF:

0.669

AC:

101747

AN:

152178

Hom.:

34653

Cov.:

AF XY:

0.671

AC XY:

49945

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.803

Gnomad4 AMR

AF:

0.689

Gnomad4 ASJ

AF:

0.651

Gnomad4 EAS

AF:

0.526

Gnomad4 SAS

AF:

0.740

Gnomad4 FIN

AF:

0.603

Gnomad4 NFE

AF:

0.598

Gnomad4 OTH

AF:

0.658

Alfa

AF:

0.633

Hom.:

5673

Bravo

AF:

0.679

Asia WGS

AF:

0.628

AC:

2188

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

-0.86

CADD

Benign

0.95

DANN

Benign

0.15

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