Variant 17-27773295-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000313735.11(NOS2):c.1477-52T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 1,358,722 control chromosomes in the GnomAD database, including 279,574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.68 ( 35728 hom., cov: 31)

Exomes 𝑓: 0.63 ( 243846 hom. )

Consequence

NOS2
ENST00000313735.11 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.62

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=-0.92).

BP6

Variant 17-27773295-A-G is Benign according to our data. Variant chr17-27773295-A-G is described in ClinVar as [Benign]. Clinvar id is 2687962.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 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.1477-52T>C		intron_variant		ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11 linkuse as main transcript	c.1477-52T>C		intron_variant		1	NM_000625.4	ENSP00000327251	P2	P35228-1

Frequencies

GnomAD3 genomes

AF:

0.679

AC:

103137

AN:

151914

Hom.:

35672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.809

Gnomad AMI

AF:

0.762

Gnomad AMR

AF:

0.663

Gnomad ASJ

AF:

0.702

Gnomad EAS

AF:

0.676

Gnomad SAS

AF:

0.800

Gnomad FIN

AF:

0.561

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.610

Gnomad OTH

AF:

0.688

GnomAD3 exomes

AF:

0.651

AC:

156524

AN:

240592

Hom.:

51918

AF XY:

0.656

AC XY:

85791

AN XY:

130766

show subpopulations

Gnomad AFR exome

AF:

0.814

Gnomad AMR exome

AF:

0.618

Gnomad ASJ exome

AF:

0.695

Gnomad EAS exome

AF:

0.679

Gnomad SAS exome

AF:

0.799

Gnomad FIN exome

AF:

0.557

Gnomad NFE exome

AF:

0.606

Gnomad OTH exome

AF:

0.651

GnomAD4 exome

AF:

0.632

AC:

762962

AN:

1206692

Hom.:

243846

Cov.:

AF XY:

0.638

AC XY:

391115

AN XY:

613298

show subpopulations

Gnomad4 AFR exome

AF:

0.824

Gnomad4 AMR exome

AF:

0.621

Gnomad4 ASJ exome

AF:

0.700

Gnomad4 EAS exome

AF:

0.727

Gnomad4 SAS exome

AF:

0.796

Gnomad4 FIN exome

AF:

0.558

Gnomad4 NFE exome

AF:

0.608

Gnomad4 OTH exome

AF:

0.653

GnomAD4 genome

AF:

0.679

AC:

103253

AN:

152030

Hom.:

35728

Cov.:

AF XY:

0.680

AC XY:

50501

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.809

Gnomad4 AMR

AF:

0.664

Gnomad4 ASJ

AF:

0.702

Gnomad4 EAS

AF:

0.676

Gnomad4 SAS

AF:

0.801

Gnomad4 FIN

AF:

0.561

Gnomad4 NFE

AF:

0.610

Gnomad4 OTH

AF:

0.690

Alfa

AF:

0.592

Hom.:

3500

Bravo

AF:

0.686

Asia WGS

AF:

0.762

AC:

2651

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 85% of patients studied by a panel of primary immunodeficiencies. Number of patients: 81. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.18

DANN

Benign

0.28

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