12-117256215-C-T

Position:

• chr12-117256215-C-T

Variant summary

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

The ENST00000317775.11(NOS1):​c.2531+2182G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 151,044 control chromosomes in the GnomAD database, including 2,616 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 0.18 (2616 hom., cov: 30)
• Consequence: NOS1 ENST00000317775.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1	NM_000620.5	c.2531+2182G>A		intron_variant		ENST00000317775.11	NP_000611.1
NOS1	NM_001204213.2	c.1523+2182G>A		intron_variant			NP_001191142.1
NOS1	NM_001204214.2	c.1523+2182G>A		intron_variant			NP_001191143.1
NOS1	NM_001204218.2	c.2532-178G>A		intron_variant			NP_001191147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1	ENST00000317775.11	c.2531+2182G>A		intron_variant		1	NM_000620.5	ENSP00000320758	P1
NOS1	ENST00000338101.8	c.2532-178G>A		intron_variant		5		ENSP00000337459
NOS1	ENST00000618760.4	c.2532-178G>A		intron_variant		5		ENSP00000477999

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26462 AN: 150938 Hom.: 2615 Cov.: 30

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.175 AC: 26475 AN: 151044 Hom.: 2616 Cov.: 30 AF XY: 0.176 AC XY: 13003 AN XY: 73728

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.205

Alfa AF: 0.184 Hom.: 744

Bravo AF: 0.171

Asia WGS AF: 0.222 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.7
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs12829185; hg19: chr12-117694020;