rs532967

Positions:

• chr12-117294534-A-G

Variant summary

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

The NM_000620.5(NOS1):​c.853-4108T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 152,060 control chromosomes in the GnomAD database, including 52,854 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 0.83 (52854 hom., cov: 31)
• Consequence: NOS1 NM_000620.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.788

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 (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1	NM_000620.5	c.853-4108T>C		intron_variant		ENST00000317775.11	NP_000611.1
NOS1	NM_001204218.2	c.853-4108T>C		intron_variant			NP_001191147.1
NOS1	NM_001204213.2	c.-156-4108T>C		intron_variant			NP_001191142.1
NOS1	NM_001204214.2	c.-156-4108T>C		intron_variant			NP_001191143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1	ENST00000317775.11	c.853-4108T>C		intron_variant		1	NM_000620.5	ENSP00000320758.6
NOS1	ENST00000338101.8	c.853-4108T>C		intron_variant		5		ENSP00000337459.4
NOS1	ENST00000618760.4	c.853-4108T>C		intron_variant		5		ENSP00000477999.1

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126506 AN: 151940 Hom.: 52807 Cov.: 31

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.833 AC: 126611 AN: 152060 Hom.: 52854 Cov.: 31 AF XY: 0.832 AC XY: 61813 AN XY: 74314

Gnomad4 AFR AF: 0.873

Gnomad4 AMR AF: 0.833

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.801

Gnomad4 SAS AF: 0.851

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.813

Gnomad4 OTH AF: 0.828

Alfa AF: 0.817 Hom.: 105981

Bravo AF: 0.838

Asia WGS AF: 0.802 AC: 2792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	15
DANN	Benign	0.77

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: rs532967; hg19: chr12-117732339;