chr7-150993921-C-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_000603.5(NOS3):​c.118C>A​(p.Arg40Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000028 in 1,428,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

NOS3
NM_000603.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.434
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP7
Synonymous conserved (PhyloP=-0.434 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NOS3NM_000603.5 linkc.118C>A p.Arg40Arg synonymous_variant Exon 2 of 27 ENST00000297494.8 NP_000594.2 P29474-1
NOS3NM_001160111.1 linkc.118C>A p.Arg40Arg synonymous_variant Exon 1 of 14 NP_001153583.1 P29474-2
NOS3NM_001160110.1 linkc.118C>A p.Arg40Arg synonymous_variant Exon 1 of 14 NP_001153582.1 P29474-3
NOS3NM_001160109.2 linkc.118C>A p.Arg40Arg synonymous_variant Exon 1 of 14 NP_001153581.1 P29474A0S0A6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NOS3ENST00000297494.8 linkc.118C>A p.Arg40Arg synonymous_variant Exon 2 of 27 1 NM_000603.5 ENSP00000297494.3 P29474-1
NOS3ENST00000484524.5 linkc.118C>A p.Arg40Arg synonymous_variant Exon 1 of 14 1 ENSP00000420215.1 P29474-2
NOS3ENST00000467517.1 linkc.118C>A p.Arg40Arg synonymous_variant Exon 1 of 14 1 ENSP00000420551.1 P29474-3
NOS3ENST00000461406.5 linkc.-148-1282C>A intron_variant Intron 1 of 23 2 ENSP00000417143.1 E7ESA7

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000280
AC:
4
AN:
1428664
Hom.:
0
Cov.:
31
AF XY:
0.00000282
AC XY:
2
AN XY:
708210
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000365
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
4.2
DANN
Benign
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-150691009; COSMIC: COSV99872320; API