rs561712

chr12-117314264-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.726-2672G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,012 control chromosomes in the GnomAD database, including 11,389 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 0.38 (11389 hom., cov: 32)
• Consequence: NOS1 NM_000620.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1	NM_000620.5	c.726-2672G>A		intron_variant		ENST00000317775.11
NOS1	NM_001204218.2	c.726-2672G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1	ENST00000317775.11	c.726-2672G>A		intron_variant		1	NM_000620.5	P1
NOS1	ENST00000338101.8	c.726-2672G>A		intron_variant		5
NOS1	ENST00000618760.4	c.726-2672G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57743 AN: 151894 Hom.: 11380 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.380 AC: 57777 AN: 152012 Hom.: 11389 Cov.: 32 AF XY: 0.379 AC XY: 28125 AN XY: 74298

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.378

Alfa AF: 0.378 Hom.: 7655

Bravo AF: 0.374

Asia WGS AF: 0.302 AC: 1049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.9
Dann	Benign	0.69

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: rs561712; hg19: chr12-117752069;