rs1047735
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_000620.5(NOS1):c.2706C>T(p.His902=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,611,784 control chromosomes in the GnomAD database, including 82,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.30 ( 7477 hom., cov: 30)
Exomes 𝑓: 0.31 ( 74825 hom. )
Consequence
NOS1
NM_000620.5 synonymous
NM_000620.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.37
Genes affected
NOS1 (HGNC:7872): (nitric oxide synthase 1) The protein encoded by this gene belongs to the family of nitric oxide synthases, which synthesize nitric oxide from L-arginine. Nitric oxide is a reactive free radical, which acts as a biologic mediator in several processes, including neurotransmission, and antimicrobial and antitumoral activities. In the brain and peripheral nervous system, nitric oxide displays many properties of a neurotransmitter, and has been implicated in neurotoxicity associated with stroke and neurodegenerative diseases, neural regulation of smooth muscle, including peristalsis, and penile erection. This protein is ubiquitously expressed, with high level of expression in skeletal muscle. Multiple transcript variants that differ in the 5' UTR have been described for this gene but the full-length nature of these transcripts is not known. Additionally, alternatively spliced transcript variants encoding different isoforms (some testis-specific) have been found for this gene.[provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 12-117247465-G-A is Benign according to our data. Variant chr12-117247465-G-A is described in ClinVar as [Benign]. Clinvar id is 3060800.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.37 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOS1 | NM_000620.5 | c.2706C>T | p.His902= | synonymous_variant | 18/29 | ENST00000317775.11 | |
NOS1 | NM_001204218.2 | c.2808C>T | p.His936= | synonymous_variant | 19/30 | ||
NOS1 | NM_001204213.2 | c.1698C>T | p.His566= | synonymous_variant | 17/28 | ||
NOS1 | NM_001204214.2 | c.1698C>T | p.His566= | synonymous_variant | 17/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOS1 | ENST00000317775.11 | c.2706C>T | p.His902= | synonymous_variant | 18/29 | 1 | NM_000620.5 | P1 | |
NOS1 | ENST00000338101.8 | c.2808C>T | p.His936= | synonymous_variant | 18/29 | 5 | |||
NOS1 | ENST00000618760.4 | c.2808C>T | p.His936= | synonymous_variant | 19/30 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.296 AC: 44776AN: 151302Hom.: 7453 Cov.: 30
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GnomAD3 exomes AF: 0.350 AC: 86657AN: 247758Hom.: 17160 AF XY: 0.341 AC XY: 45811AN XY: 134432
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GnomAD4 exome AF: 0.313 AC: 457509AN: 1460364Hom.: 74825 Cov.: 35 AF XY: 0.313 AC XY: 227195AN XY: 726476
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GnomAD4 genome ? AF: 0.296 AC: 44823AN: 151420Hom.: 7477 Cov.: 30 AF XY: 0.299 AC XY: 22117AN XY: 73932
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
NOS1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 18, 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at