rs3918169

Positions:

• chr7-150997518-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.582+593A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,006 control chromosomes in the GnomAD database, including 7,155 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 0.26 (7155 hom., cov: 31)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.582+593A>G		intron_variant		ENST00000297494.8	NP_000594.2
NOS3	NM_001160109.2	c.582+593A>G		intron_variant			NP_001153581.1
NOS3	NM_001160110.1	c.582+593A>G		intron_variant			NP_001153582.1
NOS3	NM_001160111.1	c.582+593A>G		intron_variant			NP_001153583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.582+593A>G		intron_variant		1	NM_000603.5	ENSP00000297494	P1
NOS3	ENST00000467517.1	c.582+593A>G		intron_variant		1		ENSP00000420551
NOS3	ENST00000484524.5	c.582+593A>G		intron_variant		1		ENSP00000420215
NOS3	ENST00000461406.5	c.-36-839A>G		intron_variant		2		ENSP00000417143

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39451 AN: 151886 Hom.: 7124 Cov.: 31

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.260 AC: 39520 AN: 152006 Hom.: 7155 Cov.: 31 AF XY: 0.257 AC XY: 19116 AN XY: 74306

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.237

Alfa AF: 0.202 Hom.: 1053

Bravo AF: 0.268

Asia WGS AF: 0.173 AC: 604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.92
DANN	Benign	0.42

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: rs3918169; hg19: chr7-150694606;