12-117409135-G-T

Variant names:

• chr12-117409135-G-T
• rs10774914
• ENST00000549189.1:n.470+42566C>A

Variant summary

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

The ENST00000549189.1(NOS1):​n.470+42566C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 151,994 control chromosomes in the GnomAD database, including 32,368 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 0.63 (32368 hom., cov: 31)
• Consequence: NOS1 ENST00000549189.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 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.470+42566C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95832 AN: 151876 Hom.: 32325 Cov.: 31

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.631 AC: 95934 AN: 151994 Hom.: 32368 Cov.: 31 AF XY: 0.632 AC XY: 46971 AN XY: 74270

African (AFR) AF: 0.849 AC: 35220 AN: 41474

American (AMR) AF: 0.610 AC: 9326 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1680 AN: 3466

East Asian (EAS) AF: 0.889 AC: 4573 AN: 5144

South Asian (SAS) AF: 0.776 AC: 3738 AN: 4818

European-Finnish (FIN) AF: 0.479 AC: 5052 AN: 10556

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34444 AN: 67938

Other (OTH) AF: 0.603 AC: 1274 AN: 2112

Alfa AF: 0.517 Hom.: 17472

Bravo AF: 0.645

Asia WGS AF: 0.829 AC: 2877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.39
DANN	Benign	0.16
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs10774914; hg19: chr12-117846940;