12-117367070-T-C

Variant names:

• chr12-117367070-T-C
• rs4767535
• ENST00000549189.1:n.471-35581A>G

Variant summary

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

The ENST00000549189.1(NOS1):​n.471-35581A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,012 control chromosomes in the GnomAD database, including 14,838 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 0.44 (14838 hom., cov: 32)
• Consequence: NOS1 ENST00000549189.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 14 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1	ENST00000549189.1	TSL:3	n.471-35581A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66481 AN: 151894 Hom.: 14823 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.438 AC: 66536 AN: 152012 Hom.: 14838 Cov.: 32 AF XY: 0.435 AC XY: 32333 AN XY: 74280

African (AFR) AF: 0.404 AC: 16728 AN: 41434

American (AMR) AF: 0.455 AC: 6953 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1489 AN: 3472

East Asian (EAS) AF: 0.583 AC: 3008 AN: 5158

South Asian (SAS) AF: 0.413 AC: 1991 AN: 4820

European-Finnish (FIN) AF: 0.393 AC: 4152 AN: 10556

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30893 AN: 67966

Other (OTH) AF: 0.444 AC: 937 AN: 2110

Alfa AF: 0.452 Hom.: 68232

Bravo AF: 0.445

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.37
PhyloP100		0.010

Splicing

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

Other links and lift over

dbSNP: rs4767535; hg19: chr12-117804875;