rs816296

chr12-117332939-A-Cchr12-117332939-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000620.5(NOS1):c.-420-1450T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,158 control chromosomes in the GnomAD database, including 45,699 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 0.77 (45699 hom., cov: 33)
• Consequence: NOS1 NM_000620.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1	NM_000620.5	c.-420-1450T>G		intron_variant		ENST00000317775.11
NOS1	NM_001204218.2	c.-420-1450T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1	ENST00000317775.11	c.-420-1450T>G		intron_variant		1	NM_000620.5	P1
NOS1	ENST00000618760.4	c.-420-1450T>G		intron_variant		5
NOS1	ENST00000549189.1	n.471-1450T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117292 AN: 152040 Hom.: 45667 Cov.: 33

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.771 AC: 117375 AN: 152158 Hom.: 45699 Cov.: 33 AF XY: 0.770 AC XY: 57308 AN XY: 74386

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.804

Gnomad4 ASJ AF: 0.836

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.856

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.817

Gnomad4 OTH AF: 0.786

Alfa AF: 0.814 Hom.: 33934

Bravo AF: 0.767

Asia WGS AF: 0.760 AC: 2644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	2.2
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs816296; hg19: chr12-117770744;