rs3918174

Positions:

• chr7-151000206-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.1132-292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 151,798 control chromosomes in the GnomAD database, including 1,637 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 0.14 (1637 hom., cov: 30)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS3	NM_000603.5	c.1132-292A>G		intron_variant		ENST00000297494.8
NOS3	NM_001160109.2	c.1132-292A>G		intron_variant
NOS3	NM_001160110.1	c.1132-292A>G		intron_variant
NOS3	NM_001160111.1	c.1132-292A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8	c.1132-292A>G		intron_variant		1	NM_000603.5	P1
NOS3	ENST00000467517.1	c.1132-292A>G		intron_variant		1
NOS3	ENST00000484524.5	c.1132-292A>G		intron_variant		1
NOS3	ENST00000461406.5	c.514-292A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21127 AN: 151680 Hom.: 1637 Cov.: 30

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0916

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.139 AC: 21119 AN: 151798 Hom.: 1637 Cov.: 30 AF XY: 0.140 AC XY: 10395 AN XY: 74190

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0916

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.139

Alfa AF: 0.149 Hom.: 305

Bravo AF: 0.131

Asia WGS AF: 0.128 AC: 444 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.0
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3918174; hg19: chr7-150697294;