chr12-117439680-C-T

Variant names:

• chr12-117439680-C-T
• rs41279104
• ENST00000549189.1:n.470+12021G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000549189.1(NOS1):​n.470+12021G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,218 control chromosomes in the GnomAD database, including 918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.11 (918 hom., cov: 33)
• Consequence: NOS1 ENST00000549189.1 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.408
• Publications: 32 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.163 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+12021G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16173 AN: 152100 Hom.: 917 Cov.: 33

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0896

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.106 AC: 16185 AN: 152218 Hom.: 918 Cov.: 33 AF XY: 0.107 AC XY: 7979 AN XY: 74404

African (AFR) AF: 0.0855 AC: 3552 AN: 41540

American (AMR) AF: 0.0896 AC: 1371 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 387 AN: 3472

East Asian (EAS) AF: 0.173 AC: 890 AN: 5148

South Asian (SAS) AF: 0.0816 AC: 394 AN: 4830

European-Finnish (FIN) AF: 0.145 AC: 1538 AN: 10606

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7632 AN: 67996

Other (OTH) AF: 0.113 AC: 239 AN: 2114

Alfa AF: 0.112 Hom.: 133

Bravo AF: 0.103

Asia WGS AF: 0.111 AC: 386 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Pyloric stenosis, infantile hypertrophic, 1 Uncertain:1

Dec 01, 2009

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.74
PhyloP100		0.41

Splicing

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

Other links and lift over

dbSNP: rs41279104; hg19: chr12-117877485;