chr12-117217326-C-G

Position:

• chr12-117217326-C-G

Variant summary

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

The NM_000620.5(NOS1):​c.4289+720G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,000 control chromosomes in the GnomAD database, including 5,469 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 0.27 (5469 hom., cov: 31)
• Consequence: NOS1 NM_000620.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1	NM_000620.5	c.4289+720G>C		intron_variant		ENST00000317775.11
NOS1	NM_001204213.2	c.3281+720G>C		intron_variant
NOS1	NM_001204214.2	c.3281+720G>C		intron_variant
NOS1	NM_001204218.2	c.4391+720G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1	ENST00000317775.11	c.4289+720G>C		intron_variant		1	NM_000620.5	P1
NOS1	ENST00000338101.8	c.4391+720G>C		intron_variant		5
NOS1	ENST00000618760.4	c.4391+720G>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40477 AN: 151882 Hom.: 5462 Cov.: 31

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.266 AC: 40505 AN: 152000 Hom.: 5469 Cov.: 31 AF XY: 0.269 AC XY: 19986 AN XY: 74276

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.291

Alfa AF: 0.269 Hom.: 671

Bravo AF: 0.261

Asia WGS AF: 0.335 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.78

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: rs816361; hg19: chr12-117655131;