rs3825102

Positions:

• chr12-117282380-C-A

Variant summary

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

The NM_000620.5(NOS1):​c.1383-1514G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,028 control chromosomes in the GnomAD database, including 7,659 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 0.30 (7659 hom., cov: 32)
• Consequence: NOS1 NM_000620.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1	NM_000620.5	c.1383-1514G>T		intron_variant		ENST00000317775.11	NP_000611.1
NOS1	NM_001204213.2	c.375-1514G>T		intron_variant			NP_001191142.1
NOS1	NM_001204214.2	c.375-1514G>T		intron_variant			NP_001191143.1
NOS1	NM_001204218.2	c.1383-1514G>T		intron_variant			NP_001191147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1	ENST00000317775.11	c.1383-1514G>T		intron_variant		1	NM_000620.5	ENSP00000320758	P1
NOS1	ENST00000338101.8	c.1383-1514G>T		intron_variant		5		ENSP00000337459
NOS1	ENST00000618760.4	c.1383-1514G>T		intron_variant		5		ENSP00000477999

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46271 AN: 151910 Hom.: 7658 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.304 AC: 46281 AN: 152028 Hom.: 7659 Cov.: 32 AF XY: 0.306 AC XY: 22742 AN XY: 74328

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.317

Alfa AF: 0.351 Hom.: 19499

Bravo AF: 0.291

Asia WGS AF: 0.278 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.37

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: rs3825102; hg19: chr12-117720185;