rs7977109

chr12-117292535-G-Achr12-117292535-G-Cchr12-117292535-G-T

Variant summary

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

The NM_000620.5(NOS1):c.853-2109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 152,026 control chromosomes in the GnomAD database, including 28,931 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 0.60 (28931 hom., cov: 32)
• Consequence: NOS1 NM_000620.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1	NM_000620.5	c.853-2109C>T		intron_variant		ENST00000317775.11
NOS1	NM_001204213.2	c.-156-2109C>T		intron_variant
NOS1	NM_001204214.2	c.-156-2109C>T		intron_variant
NOS1	NM_001204218.2	c.853-2109C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1	ENST00000317775.11	c.853-2109C>T		intron_variant		1	NM_000620.5	P1
NOS1	ENST00000338101.8	c.853-2109C>T		intron_variant		5
NOS1	ENST00000618760.4	c.853-2109C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90802 AN: 151908 Hom.: 28892 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.598 AC: 90890 AN: 152026 Hom.: 28931 Cov.: 32 AF XY: 0.597 AC XY: 44389 AN XY: 74314

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.586

Alfa AF: 0.507 Hom.: 21196

Bravo AF: 0.597

Asia WGS AF: 0.656 AC: 2278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	3.5
Dann	Benign	0.37

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: rs7977109; hg19: chr12-117730340;