rs2297518
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000625.4(NOS2):c.1823C>T(p.Ser608Leu) variant causes a missense change. The variant allele was found at a frequency of 0.184 in 1,608,552 control chromosomes in the GnomAD database, including 28,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: 𝑓 0.17 ( 2373 hom., cov: 33)
Exomes 𝑓: 0.18 ( 26033 hom. )
Consequence
NOS2
NM_000625.4 missense
NM_000625.4 missense
Scores
1
5
12
Clinical Significance
Conservation
PhyloP100: 6.41
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]
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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 (MetaRNN=0.0028576553).
BP6
Variant 17-27769571-G-A is Benign according to our data. Variant chr17-27769571-G-A is described in ClinVar as [Benign]. Clinvar id is 2688228.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NOS2 | NM_000625.4 | c.1823C>T | p.Ser608Leu | missense_variant | 16/27 | ENST00000313735.11 | NP_000616.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NOS2 | ENST00000313735.11 | c.1823C>T | p.Ser608Leu | missense_variant | 16/27 | 1 | NM_000625.4 | ENSP00000327251 | P2 |
Frequencies
GnomAD3 genomes AF: 0.172 AC: 26142AN: 151996Hom.: 2375 Cov.: 33
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GnomAD3 exomes AF: 0.177 AC: 44586AN: 251380Hom.: 4216 AF XY: 0.183 AC XY: 24836AN XY: 135860
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GnomAD4 exome AF: 0.185 AC: 269171AN: 1456438Hom.: 26033 Cov.: 31 AF XY: 0.186 AC XY: 134655AN XY: 724896
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GnomAD4 genome AF: 0.172 AC: 26144AN: 152114Hom.: 2373 Cov.: 33 AF XY: 0.173 AC XY: 12838AN XY: 74374
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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 32% of patients studied by a panel of primary immunodeficiencies. Number of patients: 30. Only high quality variants are reported. - |
NOS2-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 04, 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
P
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.
REVEL
Benign
Sift
Benign
T;.;.
Sift4G
Benign
T;.;T
Polyphen
P;.;.
Vest4
MPC
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at