rs3730006

Positions:

• chr7-151009089-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.2245+27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 1,612,764 control chromosomes in the GnomAD database, including 461 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 0.021 (33 hom., cov: 33)
  • Exomes 𝑓: 0.022 (428 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.708

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=-0.88).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS3	NM_000603.5	c.2245+27G>A		intron_variant		ENST00000297494.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8	c.2245+27G>A		intron_variant		1	NM_000603.5	P1
NOS3	ENST00000461406.5	c.1627+27G>A		intron_variant		2
NOS3	ENST00000475017.1	c.126+27G>A		intron_variant		2
NOS3	ENST00000473057.1	n.189+27G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 3148 AN: 152116 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.00696

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0242

Gnomad OTH AF: 0.0460

GnomAD3 exomes AF: 0.0187 AC: 4623 AN: 246770 Hom.: 71 AF XY: 0.0189 AC XY: 2526 AN XY: 133942

Gnomad AFR exome AF: 0.0181

Gnomad AMR exome AF: 0.0194

Gnomad ASJ exome AF: 0.0314

Gnomad EAS exome AF: 0.0000550

Gnomad SAS exome AF: 0.00693

Gnomad FIN exome AF: 0.00985

Gnomad NFE exome AF: 0.0248

Gnomad OTH exome AF: 0.0319

GnomAD4 exome AF: 0.0216 AC: 31617 AN: 1460530 Hom.: 428 Cov.: 32 AF XY: 0.0215 AC XY: 15633 AN XY: 726538

Gnomad4 AFR exome AF: 0.0196

Gnomad4 AMR exome AF: 0.0204

Gnomad4 ASJ exome AF: 0.0319

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00724

Gnomad4 FIN exome AF: 0.00970

Gnomad4 NFE exome AF: 0.0235

Gnomad4 OTH exome AF: 0.0268

GnomAD4 genome AF: 0.0207 AC: 3152 AN: 152234 Hom.: 33 Cov.: 33 AF XY: 0.0197 AC XY: 1470 AN XY: 74440

Gnomad4 AFR AF: 0.0178

Gnomad4 AMR AF: 0.0275

Gnomad4 ASJ AF: 0.0280

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.00696

Gnomad4 NFE AF: 0.0242

Gnomad4 OTH AF: 0.0460

Alfa AF: 0.0246 Hom.: 17

Bravo AF: 0.0231

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.7
DANN	Benign	0.48

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: rs3730006; hg19: chr7-150706177;