rs2853792

Positions:

• chr7-151002789-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.1752+485G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 201,112 control chromosomes in the GnomAD database, including 47,803 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 0.69 (36424 hom., cov: 32)
  • Exomes 𝑓: 0.68 (11379 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS3	NM_000603.5	c.1752+485G>A		intron_variant		ENST00000297494.8
NOS3	NM_001160109.2	c.1752+485G>A		intron_variant
NOS3	NM_001160110.1	c.1752+485G>A		intron_variant
NOS3	NM_001160111.1	c.1753-362G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8	c.1752+485G>A		intron_variant		1	NM_000603.5	P1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104048 AN: 151924 Hom.: 36365 Cov.: 32

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.674

GnomAD4 exome AF: 0.676 AC: 33184 AN: 49070 Hom.: 11379 Cov.: 0 AF XY: 0.682 AC XY: 17463 AN XY: 25624

Gnomad4 AFR exome AF: 0.839

Gnomad4 AMR exome AF: 0.732

Gnomad4 ASJ exome AF: 0.728

Gnomad4 EAS exome AF: 0.740

Gnomad4 SAS exome AF: 0.725

Gnomad4 FIN exome AF: 0.650

Gnomad4 NFE exome AF: 0.652

Gnomad4 OTH exome AF: 0.663

GnomAD4 genome AF: 0.685 AC: 104161 AN: 152042 Hom.: 36424 Cov.: 32 AF XY: 0.685 AC XY: 50888 AN XY: 74334

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.688

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.669

Alfa AF: 0.625 Hom.: 28633

Bravo AF: 0.698

Asia WGS AF: 0.688 AC: 2392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.056
DANN	Benign	0.20

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: rs2853792; hg19: chr7-150699877;