rs3918226

Positions:

• chr7-150993088-C-T

Variant summary

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

The NM_000603.5(NOS3):​c.-51-665C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0563 in 152,272 control chromosomes in the GnomAD database, including 350 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 0.056 (350 hom., cov: 33)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.903

Genes affected

NOS3 (HGNC:7876): (nitric oxide synthase 3) Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. Nitric oxide is synthesized from L-arginine by nitric oxide synthases. Variations in this gene are associated with susceptibility to coronary spasm. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.-51-665C>T		intron_variant		ENST00000297494.8	NP_000594.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.-51-665C>T		intron_variant		1	NM_000603.5	ENSP00000297494	P1
NOS3	ENST00000461406.5	c.-149+1788C>T		intron_variant		2		ENSP00000417143

Frequencies

GnomAD3 genomes AF: 0.0564 AC: 8577 AN: 152154 Hom.: 350 Cov.: 33

Gnomad AFR AF: 0.0152

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.0786

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0826

Gnomad OTH AF: 0.0641

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

GnomAD4 genome AF: 0.0563 AC: 8575 AN: 152272 Hom.: 350 Cov.: 33 AF XY: 0.0546 AC XY: 4068 AN XY: 74452

Gnomad4 AFR AF: 0.0151

Gnomad4 AMR AF: 0.0667

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00932

Gnomad4 FIN AF: 0.0786

Gnomad4 NFE AF: 0.0826

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0797 Hom.: 437

Bravo AF: 0.0530

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	19
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs3918226; hg19: chr7-150690176;