rs3782206

Variant names:

• chr12-117307284-C-T
• rs3782206
• NM_000620.5:c.852+4182G>A

Variant summary

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

The NM_000620.5(NOS1):​c.852+4182G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,144 control chromosomes in the GnomAD database, including 1,313 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 0.12 (1313 hom., cov: 32)
• Consequence: NOS1 NM_000620.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 18 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1	NM_000620.5	c.852+4182G>A		intron_variant	Intron 3 of 28	ENST00000317775.11	NP_000611.1
NOS1	NM_001204218.2	c.852+4182G>A		intron_variant	Intron 3 of 29		NP_001191147.1
NOS1	NM_001204214.2	c.-213+2033G>A		intron_variant	Intron 1 of 27		NP_001191143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1	ENST00000317775.11	c.852+4182G>A		intron_variant	Intron 3 of 28	1	NM_000620.5	ENSP00000320758.6
NOS1	ENST00000338101.8	c.852+4182G>A		intron_variant	Intron 2 of 28	5		ENSP00000337459.4
NOS1	ENST00000618760.4	c.852+4182G>A		intron_variant	Intron 3 of 29	5		ENSP00000477999.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17731 AN: 152026 Hom.: 1311 Cov.: 32

Gnomad AFR AF: 0.0569

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.117 AC: 17742 AN: 152144 Hom.: 1313 Cov.: 32 AF XY: 0.121 AC XY: 8967 AN XY: 74366

African (AFR) AF: 0.0568 AC: 2358 AN: 41522

American (AMR) AF: 0.184 AC: 2816 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3466

East Asian (EAS) AF: 0.244 AC: 1258 AN: 5162

South Asian (SAS) AF: 0.225 AC: 1085 AN: 4826

European-Finnish (FIN) AF: 0.113 AC: 1191 AN: 10568

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8233 AN: 68008

Other (OTH) AF: 0.131 AC: 276 AN: 2114

Alfa AF: 0.122 Hom.: 1365

Bravo AF: 0.115

Asia WGS AF: 0.195 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.2
DANN	Benign	0.70
PhyloP100		0.19
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: rs3782206; hg19: chr12-117745089;