12-117367070-T-C

Position:

• chr12-117367070-T-C

Variant summary

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

The ENST00000549189.1(NOS1):​n.471-35581A>G 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 0.438 in 152,012 control chromosomes in the GnomAD database, including 14,838 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 0.44 (14838 hom., cov: 32)
• Consequence: NOS1 ENST00000549189.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 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.471-35581A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66481 AN: 151894 Hom.: 14823 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.438 AC: 66536 AN: 152012 Hom.: 14838 Cov.: 32 AF XY: 0.435 AC XY: 32333 AN XY: 74280

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.444

Alfa AF: 0.454 Hom.: 36367

Bravo AF: 0.445

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4767535; hg19: chr12-117804875;