rs2853795

Positions:

• chr7-151006154-A-G

Variant summary

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

The NM_000603.5(NOS3):​c.1753-273A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,180 control chromosomes in the GnomAD database, including 2,851 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 0.16 (2851 hom., cov: 33)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS3	NM_000603.5	c.1753-273A>G		intron_variant		ENST00000297494.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8	c.1753-273A>G		intron_variant		1	NM_000603.5	P1
NOS3	ENST00000461406.5	c.1135-273A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 25014 AN: 152062 Hom.: 2837 Cov.: 33

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.165 AC: 25043 AN: 152180 Hom.: 2851 Cov.: 33 AF XY: 0.171 AC XY: 12727 AN XY: 74408

Gnomad4 AFR AF: 0.0505

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.161

Alfa AF: 0.176 Hom.: 2756

Bravo AF: 0.172

Asia WGS AF: 0.228 AC: 792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.66

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: rs2853795; hg19: chr7-150703242;