12-117365710-C-T

Variant names:

• chr12-117365710-C-T
• rs1879417
• ENST00000549189.1:n.471-34221G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000549189.1(NOS1):​n.471-34221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 151,948 control chromosomes in the GnomAD database, including 23,801 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 0.56 (23801 hom., cov: 32)
• Consequence: NOS1 ENST00000549189.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740
• Publications: 25 publications found

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]

NOS1 Gene-Disease associations (from GenCC):

• idiopathic achalasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1	ENST00000549189.1	n.471-34221G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84505 AN: 151830 Hom.: 23772 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.515

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.557 AC: 84593 AN: 151948 Hom.: 23801 Cov.: 32 AF XY: 0.556 AC XY: 41293 AN XY: 74264

African (AFR) AF: 0.595 AC: 24656 AN: 41448

American (AMR) AF: 0.544 AC: 8299 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1835 AN: 3470

East Asian (EAS) AF: 0.505 AC: 2599 AN: 5146

South Asian (SAS) AF: 0.420 AC: 2021 AN: 4812

European-Finnish (FIN) AF: 0.598 AC: 6315 AN: 10556

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.550 AC: 37346 AN: 67938

Other (OTH) AF: 0.520 AC: 1097 AN: 2110

Alfa AF: 0.544 Hom.: 47078

Bravo AF: 0.557

Asia WGS AF: 0.496 AC: 1726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.15
DANN	Benign	0.76
PhyloP100		-0.74

Splicing

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

Other links and lift over

dbSNP: rs1879417; hg19: chr12-117803515;