rs11068458

chr12-117364937-A-G

Variant summary

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

The ENST00000549189.1(NOS1):n.471-33448T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,192 control chromosomes in the GnomAD database, including 1,743 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 0.11 (1743 hom., cov: 32)
• Consequence: NOS1 ENST00000549189.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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 (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1	ENST00000549189.1	n.471-33448T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17392 AN: 152074 Hom.: 1737 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0721

Gnomad ASJ AF: 0.0622

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.0354

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.0996

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

GnomAD4 genome AF: 0.115 AC: 17427 AN: 152192 Hom.: 1743 Cov.: 32 AF XY: 0.111 AC XY: 8281 AN XY: 74424

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.0720

Gnomad4 ASJ AF: 0.0622

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0641

Gnomad4 FIN AF: 0.0354

Gnomad4 NFE AF: 0.0499

Gnomad4 OTH AF: 0.0986

Alfa AF: 0.0611 Hom.: 623

Bravo AF: 0.124

Asia WGS AF: 0.0770 AC: 268 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	0.049
Dann	Benign	0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11068458; hg19: chr12-117802742;