rs3782202

Variant names:

• chr12-117282575-G-A
• rs3782202
• NM_000620.5:c.1383-1709C>T

Variant summary

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

The NM_000620.5(NOS1):​c.1383-1709C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,162 control chromosomes in the GnomAD database, including 51,480 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 0.82 (51480 hom., cov: 32)
• Consequence: NOS1 NM_000620.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 6 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1	NM_000620.5	c.1383-1709C>T		intron_variant	Intron 7 of 28	ENST00000317775.11	NP_000611.1
NOS1	NM_001204218.2	c.1383-1709C>T		intron_variant	Intron 7 of 29		NP_001191147.1
NOS1	NM_001204213.2	c.375-1709C>T		intron_variant	Intron 6 of 27		NP_001191142.1
NOS1	NM_001204214.2	c.375-1709C>T		intron_variant	Intron 6 of 27		NP_001191143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1	ENST00000317775.11	c.1383-1709C>T		intron_variant	Intron 7 of 28	1	NM_000620.5	ENSP00000320758.6
NOS1	ENST00000338101.8	c.1383-1709C>T		intron_variant	Intron 6 of 28	5		ENSP00000337459.4
NOS1	ENST00000618760.4	c.1383-1709C>T		intron_variant	Intron 7 of 29	5		ENSP00000477999.1

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124960 AN: 152044 Hom.: 51439 Cov.: 32

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.816

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

GnomAD4 genome AF: 0.822 AC: 125056 AN: 152162 Hom.: 51480 Cov.: 32 AF XY: 0.820 AC XY: 61039 AN XY: 74398

African (AFR) AF: 0.874 AC: 36272 AN: 41518

American (AMR) AF: 0.823 AC: 12563 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 2794 AN: 3472

East Asian (EAS) AF: 0.847 AC: 4378 AN: 5166

South Asian (SAS) AF: 0.843 AC: 4072 AN: 4828

European-Finnish (FIN) AF: 0.780 AC: 8268 AN: 10600

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.794 AC: 54007 AN: 67994

Other (OTH) AF: 0.815 AC: 1719 AN: 2110

Alfa AF: 0.804 Hom.: 131173

Bravo AF: 0.829

Asia WGS AF: 0.802 AC: 2793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.81
PhyloP100		-1.3
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: rs3782202; hg19: chr12-117720380; COSMIC: COSV57623340;