rs2682826

chr12-117215033-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000620.5(NOS1):c.*276C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,182,334 control chromosomes in the GnomAD database, including 43,705 homozygotes. 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: 𝑓 0.25 (5037 hom., cov: 33)
  • Exomes 𝑓: 0.27 (38668 hom.)
• Consequence: NOS1 NM_000620.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1	NM_000620.5	c.*276C>T		3_prime_UTR_variant	29/29	ENST00000317775.11
NOS1	NM_001204213.2	c.*276C>T		3_prime_UTR_variant	28/28
NOS1	NM_001204214.2	c.*276C>T		3_prime_UTR_variant	28/28
NOS1	NM_001204218.2	c.*276C>T		3_prime_UTR_variant	30/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1	ENST00000317775.11	c.*276C>T		3_prime_UTR_variant	29/29	1	NM_000620.5	P1
NOS1	ENST00000618760.4	c.*276C>T		3_prime_UTR_variant	30/30	5

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38483 AN: 152068 Hom.: 5030 Cov.: 33

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.272 AC: 280463 AN: 1030148 Hom.: 38668 Cov.: 34 AF XY: 0.273 AC XY: 132299 AN XY: 484386

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.315

Gnomad4 EAS exome AF: 0.338

Gnomad4 SAS exome AF: 0.249

Gnomad4 FIN exome AF: 0.302

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.279

GnomAD4 genome AF: 0.253 AC: 38511 AN: 152186 Hom.: 5037 Cov.: 33 AF XY: 0.256 AC XY: 19036 AN XY: 74396

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.281

Alfa AF: 0.274 Hom.: 8390

Bravo AF: 0.245

Asia WGS AF: 0.321 AC: 1114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.52
Dann	Benign	0.83

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

Other links and lift over

dbSNP: rs2682826; hg19: chr12-117652838;