Variant 17-27765529-G-A 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.2428+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 1,588,414 control chromosomes in the GnomAD database, including 322,144 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.68 ( 35219 hom., cov: 33)

Exomes 𝑓: 0.63 ( 286925 hom. )

Consequence

NOS2
NM_000625.4 splice_region, intron

Scores

Splicing: ADA: 0.0001130

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.158

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 17-27765529-G-A is Benign according to our data. Variant chr17-27765529-G-A is described in ClinVar as [Benign]. Clinvar id is 2687956.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.812 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.2428+6C>T		splice_region_variant, 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.2428+6C>T		splice_region_variant, intron_variant		1	NM_000625.4	ENSP00000327251.6		P35228-1

Frequencies

GnomAD3 genomes

AF:

0.675

AC:

102615

AN:

152026

Hom.:

35165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.780

Gnomad AMI

AF:

0.763

Gnomad AMR

AF:

0.662

Gnomad ASJ

AF:

0.686

Gnomad EAS

AF:

0.692

Gnomad SAS

AF:

0.833

Gnomad FIN

AF:

0.591

Gnomad MID

AF:

0.801

Gnomad NFE

AF:

0.612

Gnomad OTH

AF:

0.689

GnomAD3 exomes

AF:

0.648

AC:

148417

AN:

228906

Hom.:

49108

AF XY:

0.655

AC XY:

81427

AN XY:

124312

show subpopulations

Gnomad AFR exome

AF:

0.783

Gnomad AMR exome

AF:

0.609

Gnomad ASJ exome

AF:

0.666

Gnomad EAS exome

AF:

0.687

Gnomad SAS exome

AF:

0.826

Gnomad FIN exome

AF:

0.578

Gnomad NFE exome

AF:

0.601

Gnomad OTH exome

AF:

0.647

GnomAD4 exome

AF:

0.628

AC:

902060

AN:

1436270

Hom.:

286925

Cov.:

AF XY:

0.634

AC XY:

451402

AN XY:

712348

show subpopulations

Gnomad4 AFR exome

AF:

0.792

Gnomad4 AMR exome

AF:

0.614

Gnomad4 ASJ exome

AF:

0.680

Gnomad4 EAS exome

AF:

0.730

Gnomad4 SAS exome

AF:

0.826

Gnomad4 FIN exome

AF:

0.582

Gnomad4 NFE exome

AF:

0.604

Gnomad4 OTH exome

AF:

0.652

GnomAD4 genome

AF:

0.675

AC:

102730

AN:

152144

Hom.:

35219

Cov.:

AF XY:

0.678

AC XY:

50404

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.780

Gnomad4 AMR

AF:

0.663

Gnomad4 ASJ

AF:

0.686

Gnomad4 EAS

AF:

0.692

Gnomad4 SAS

AF:

0.834

Gnomad4 FIN

AF:

0.591

Gnomad4 NFE

AF:

0.612

Gnomad4 OTH

AF:

0.690

Alfa

AF:

0.650

Hom.:

9432

Bravo

AF:

0.679

Asia WGS

AF:

0.773

AC:

2691

AN:

3478

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

-0.79

CADD

Benign

8.7

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0020

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