12-117281017-C-T

Position:

• chr12-117281017-C-T

Variant summary

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

The NM_000620.5(NOS1):​c.1383-151G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 773,530 control chromosomes in the GnomAD database, including 75,120 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 0.41 (12931 hom., cov: 32)
  • Exomes 𝑓: 0.44 (62189 hom.)
• Consequence: NOS1 NM_000620.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25

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 (AMR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1	NM_000620.5	c.1383-151G>A		intron_variant		ENST00000317775.11	NP_000611.1
NOS1	NM_001204218.2	c.1383-151G>A		intron_variant			NP_001191147.1
NOS1	NM_001204213.2	c.375-151G>A		intron_variant			NP_001191142.1
NOS1	NM_001204214.2	c.375-151G>A		intron_variant			NP_001191143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1	ENST00000317775.11	c.1383-151G>A		intron_variant		1	NM_000620.5	ENSP00000320758.6
NOS1	ENST00000338101.8	c.1383-151G>A		intron_variant		5		ENSP00000337459.4
NOS1	ENST00000618760.4	c.1383-151G>A		intron_variant		5		ENSP00000477999.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61539 AN: 151656 Hom.: 12925 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.340

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.407

GnomAD4 exome AF: 0.441 AC: 274048 AN: 621756 Hom.: 62189 AF XY: 0.442 AC XY: 140912 AN XY: 318694

Gnomad4 AFR exome AF: 0.310

Gnomad4 AMR exome AF: 0.564

Gnomad4 ASJ exome AF: 0.440

Gnomad4 EAS exome AF: 0.446

Gnomad4 SAS exome AF: 0.488

Gnomad4 FIN exome AF: 0.397

Gnomad4 NFE exome AF: 0.439

Gnomad4 OTH exome AF: 0.431

GnomAD4 genome AF: 0.406 AC: 61576 AN: 151774 Hom.: 12931 Cov.: 32 AF XY: 0.406 AC XY: 30102 AN XY: 74162

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.409

Alfa AF: 0.402 Hom.: 5572

Bravo AF: 0.410

Asia WGS AF: 0.423 AC: 1474 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	0.088
DANN	Benign	0.81

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: rs2293050; hg19: chr12-117718822;