rs2853792

Variant names:

• chr7-151002789-G-A
• rs2853792
• NM_000603.5:c.1752+485G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000603.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	NM_000603.5	MANE Select	c.1752+485G>A		intron	N/A	NP_000594.2
	NOS3	NM_001160111.1		c.1753-362G>A		intron	N/A	NP_001153583.1
	NOS3	NM_001160110.1		c.1752+485G>A		intron	N/A	NP_001153582.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.1752+485G>A		intron	N/A	ENSP00000297494.3
	NOS3	ENST00000484524.5	TSL:1	c.1753-362G>A		intron	N/A	ENSP00000420215.1
	NOS3	ENST00000467517.1	TSL:1	c.1752+485G>A		intron	N/A	ENSP00000420551.1

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

African (AFR) AF: 0.839 AC: 364 AN: 434

American (AMR) AF: 0.732 AC: 2203 AN: 3010

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 827 AN: 1136

East Asian (EAS) AF: 0.740 AC: 896 AN: 1210

South Asian (SAS) AF: 0.725 AC: 6394 AN: 8816

European-Finnish (FIN) AF: 0.650 AC: 1855 AN: 2856

Middle Eastern (MID) AF: 0.663 AC: 114 AN: 172

European-Non Finnish (NFE) AF: 0.652 AC: 18726 AN: 28712

Other (OTH) AF: 0.663 AC: 1805 AN: 2724

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

African (AFR) AF: 0.818 AC: 33922 AN: 41464

American (AMR) AF: 0.688 AC: 10512 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2439 AN: 3470

East Asian (EAS) AF: 0.705 AC: 3647 AN: 5176

South Asian (SAS) AF: 0.703 AC: 3389 AN: 4822

European-Finnish (FIN) AF: 0.628 AC: 6624 AN: 10554

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41457 AN: 67964

Other (OTH) AF: 0.669 AC: 1408 AN: 2104

Alfa AF: 0.651 Hom.: 49533

Bravo AF: 0.698

Asia WGS AF: 0.688 AC: 2392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.056
DANN	Benign	0.20
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2853792; hg19: chr7-150699877;