12-117364937-A-G

Variant names:

• chr12-117364937-A-G
• rs11068458
• ENST00000549189.1:n.471-33448T>C

Variant summary

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

The ENST00000549189.1(NOS1):​n.471-33448T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,192 control chromosomes in the GnomAD database, including 1,743 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 0.11 (1743 hom., cov: 32)
• Consequence: NOS1 ENST00000549189.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000549189.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1	ENST00000549189.1	TSL:3	n.471-33448T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17392 AN: 152074 Hom.: 1737 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0721

Gnomad ASJ AF: 0.0622

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.0354

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.0996

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

GnomAD4 genome AF: 0.115 AC: 17427 AN: 152192 Hom.: 1743 Cov.: 32 AF XY: 0.111 AC XY: 8281 AN XY: 74424

African (AFR) AF: 0.270 AC: 11190 AN: 41496

American (AMR) AF: 0.0720 AC: 1102 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0622 AC: 216 AN: 3472

East Asian (EAS) AF: 0.104 AC: 538 AN: 5174

South Asian (SAS) AF: 0.0641 AC: 309 AN: 4818

European-Finnish (FIN) AF: 0.0354 AC: 376 AN: 10610

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0499 AC: 3393 AN: 67996

Other (OTH) AF: 0.0986 AC: 208 AN: 2110

Alfa AF: 0.0674 Hom.: 1230

Bravo AF: 0.124

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.049
DANN	Benign	0.29
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs11068458; hg19: chr12-117802742;