12-117398072-A-G

Variant names:

• chr12-117398072-A-G
• rs11068466
• ENST00000549189.1:n.470+53629T>C

Variant summary

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

The ENST00000549189.1(NOS1):​n.470+53629T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,184 control chromosomes in the GnomAD database, including 6,516 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 0.22 (6516 hom., cov: 32)
• Consequence: NOS1 ENST00000549189.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• Publications: 4 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 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.470+53629T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33759 AN: 152064 Hom.: 6481 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.0743

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0409

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.222 AC: 33850 AN: 152184 Hom.: 6516 Cov.: 32 AF XY: 0.215 AC XY: 16027 AN XY: 74414

African (AFR) AF: 0.521 AC: 21598 AN: 41454

American (AMR) AF: 0.160 AC: 2442 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0743 AC: 258 AN: 3472

East Asian (EAS) AF: 0.173 AC: 899 AN: 5184

South Asian (SAS) AF: 0.124 AC: 598 AN: 4820

European-Finnish (FIN) AF: 0.0409 AC: 434 AN: 10618

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7128 AN: 68018

Other (OTH) AF: 0.201 AC: 424 AN: 2112

Alfa AF: 0.140 Hom.: 10091

Bravo AF: 0.246

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		1.9

Splicing

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

Other links and lift over

dbSNP: rs11068466; hg19: chr12-117835877;