rs3793342

chr7-150998107-G-A

Variant summary

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

The NM_000603.5(NOS3):c.583-250G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,220 control chromosomes in the GnomAD database, including 1,449 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 0.13 (1449 hom., cov: 32)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS3	NM_000603.5	c.583-250G>A		intron_variant		ENST00000297494.8
NOS3	NM_001160109.2	c.583-250G>A		intron_variant
NOS3	NM_001160110.1	c.583-250G>A		intron_variant
NOS3	NM_001160111.1	c.583-250G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8	c.583-250G>A		intron_variant		1	NM_000603.5	P1
NOS3	ENST00000467517.1	c.583-250G>A		intron_variant		1
NOS3	ENST00000484524.5	c.583-250G>A		intron_variant		1
NOS3	ENST00000461406.5	c.-36-250G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19856 AN: 152102 Hom.: 1449 Cov.: 32

Gnomad AFR AF: 0.0932

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.130 AC: 19859 AN: 152220 Hom.: 1449 Cov.: 32 AF XY: 0.131 AC XY: 9762 AN XY: 74434

Gnomad4 AFR AF: 0.0933

Gnomad4 AMR AF: 0.0998

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.127

Alfa AF: 0.141 Hom.: 425

Bravo AF: 0.122

Asia WGS AF: 0.123 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.040
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3793342; hg19: chr7-150695195;