chr12-117439680-C-T

Position:

• chr12-117439680-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000549189.1(NOS1):​n.470+12021G>A 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 0.106 in 152,218 control chromosomes in the GnomAD database, including 918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.11 (918 hom., cov: 33)
• Consequence: NOS1 ENST00000549189.1 intron, non_coding_transcript
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.408

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1	ENST00000549189.1	n.470+12021G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16173 AN: 152100 Hom.: 917 Cov.: 33

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0896

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.106 AC: 16185 AN: 152218 Hom.: 918 Cov.: 33 AF XY: 0.107 AC XY: 7979 AN XY: 74404

Gnomad4 AFR AF: 0.0855

Gnomad4 AMR AF: 0.0896

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.0816

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.113

Alfa AF: 0.113 Hom.: 130

Bravo AF: 0.103

Asia WGS AF: 0.111 AC: 386 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Pyloric stenosis, infantile hypertrophic, 1 Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Dec 01, 2009

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41279104; hg19: chr12-117877485;