rs816296

Variant names:

• chr12-117332939-A-C
• rs816296
• NM_000620.5:c.-420-1450T>G

Your query was ambiguous. Multiple possible variants found:

• chr12-117332939-A-C
• chr12-117332939-A-G

Variant summary

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

The NM_000620.5(NOS1):​c.-420-1450T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,158 control chromosomes in the GnomAD database, including 45,699 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 0.77 (45699 hom., cov: 33)
• Consequence: NOS1 NM_000620.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464
• Publications: 9 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 (SAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000620.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1	NM_000620.5	MANE Select	c.-420-1450T>G		intron	N/A	NP_000611.1
	NOS1	NM_001204218.2		c.-420-1450T>G		intron	N/A	NP_001191147.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1	ENST00000317775.11	TSL:1 MANE Select	c.-420-1450T>G		intron	N/A	ENSP00000320758.6
	NOS1	ENST00000618760.4	TSL:5	c.-420-1450T>G		intron	N/A	ENSP00000477999.1
	NOS1	ENST00000549189.1	TSL:3	n.471-1450T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117292 AN: 152040 Hom.: 45667 Cov.: 33

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.771 AC: 117375 AN: 152158 Hom.: 45699 Cov.: 33 AF XY: 0.770 AC XY: 57308 AN XY: 74386

African (AFR) AF: 0.679 AC: 28172 AN: 41506

American (AMR) AF: 0.804 AC: 12303 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2904 AN: 3472

East Asian (EAS) AF: 0.637 AC: 3281 AN: 5152

South Asian (SAS) AF: 0.856 AC: 4125 AN: 4820

European-Finnish (FIN) AF: 0.792 AC: 8376 AN: 10582

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55559 AN: 68014

Other (OTH) AF: 0.786 AC: 1661 AN: 2112

Alfa AF: 0.813 Hom.: 46624

Bravo AF: 0.767

Asia WGS AF: 0.760 AC: 2644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.2
DANN	Benign	0.47
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs816296; hg19: chr12-117770744;