12-117209598-G-A

Position:

• chr12-117209598-G-A

Variant summary

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

The NM_000620.5(NOS1):​c.*5711C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 985,350 control chromosomes in the GnomAD database, including 58,381 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 0.46 (21045 hom., cov: 33)
  • Exomes 𝑓: 0.29 (37336 hom.)
• Consequence: NOS1 NM_000620.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1	NM_000620.5	c.*5711C>T		3_prime_UTR_variant	29/29	ENST00000317775.11	NP_000611.1
NOS1	NM_001204213.2	c.*5711C>T		3_prime_UTR_variant	28/28		NP_001191142.1
NOS1	NM_001204214.2	c.*5711C>T		3_prime_UTR_variant	28/28		NP_001191143.1
NOS1	NM_001204218.2	c.*5711C>T		3_prime_UTR_variant	30/30		NP_001191147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1	ENST00000317775.11	c.*5711C>T		3_prime_UTR_variant	29/29	1	NM_000620.5	ENSP00000320758	P1
NOS1	ENST00000618760.4	c.*5711C>T		3_prime_UTR_variant	30/30	5		ENSP00000477999

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69333 AN: 152112 Hom.: 20980 Cov.: 33

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.389

GnomAD4 exome AF: 0.286 AC: 237931 AN: 833118 Hom.: 37336 Cov.: 31 AF XY: 0.284 AC XY: 109422 AN XY: 384722

Gnomad4 AFR exome AF: 0.905

Gnomad4 AMR exome AF: 0.420

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.492

Gnomad4 SAS exome AF: 0.238

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.302

GnomAD4 genome AF: 0.456 AC: 69461 AN: 152232 Hom.: 21045 Cov.: 33 AF XY: 0.452 AC XY: 33674 AN XY: 74434

Gnomad4 AFR AF: 0.859

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.392

Alfa AF: 0.361 Hom.: 5482

Bravo AF: 0.493

Asia WGS AF: 0.401 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.59
DANN	Benign	0.74

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: rs10774907; hg19: chr12-117647403;