rs3918211
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000603.5(NOS3):āc.3351T>Cā(p.Val1117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00931 in 1,609,760 control chromosomes in the GnomAD database, including 938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.045 ( 495 hom., cov: 33)
Exomes š: 0.0056 ( 443 hom. )
Consequence
NOS3
NM_000603.5 synonymous
NM_000603.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.14
Genes affected
NOS3 (HGNC:7876): (nitric oxide synthase 3) Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. Nitric oxide is synthesized from L-arginine by nitric oxide synthases. Variations in this gene are associated with susceptibility to coronary spasm. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]
ATG9B (HGNC:21899): (autophagy related 9B) This gene functions in the regulation of autophagy, a lysosomal degradation pathway. This gene also functions as an antisense transcript in the posttranscriptional regulation of the endothelial nitric oxide synthase 3 gene, which has 3' overlap with this gene on the opposite strand. Mutations in this gene and disruption of the autophagy process have been associated with multiple cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 7-151013819-T-C is Benign according to our data. Variant chr7-151013819-T-C is described in ClinVar as [Benign]. Clinvar id is 403252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.14 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOS3 | NM_000603.5 | c.3351T>C | p.Val1117= | synonymous_variant | 26/27 | ENST00000297494.8 | |
ATG9B | NR_073169.1 | n.2551A>G | non_coding_transcript_exon_variant | 17/18 | |||
ATG9B | NR_133652.1 | n.3288A>G | non_coding_transcript_exon_variant | 16/17 | |||
ATG9B | XR_007060009.1 | n.3331A>G | non_coding_transcript_exon_variant | 14/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOS3 | ENST00000297494.8 | c.3351T>C | p.Val1117= | synonymous_variant | 26/27 | 1 | NM_000603.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0444 AC: 6763AN: 152182Hom.: 491 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
6763
AN:
152182
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0137 AC: 3273AN: 239072Hom.: 201 AF XY: 0.0108 AC XY: 1406AN XY: 129888
GnomAD3 exomes
AF:
AC:
3273
AN:
239072
Hom.:
AF XY:
AC XY:
1406
AN XY:
129888
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00562 AC: 8195AN: 1457460Hom.: 443 Cov.: 35 AF XY: 0.00527 AC XY: 3816AN XY: 724776
GnomAD4 exome
AF:
AC:
8195
AN:
1457460
Hom.:
Cov.:
35
AF XY:
AC XY:
3816
AN XY:
724776
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0446 AC: 6794AN: 152300Hom.: 495 Cov.: 33 AF XY: 0.0432 AC XY: 3214AN XY: 74474
GnomAD4 genome
?
AF:
AC:
6794
AN:
152300
Hom.:
Cov.:
33
AF XY:
AC XY:
3214
AN XY:
74474
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
85
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at