7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACAC

Position:

• chr7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000603.5(NOS3):​c.1752+142_1752+149del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 270,812 control chromosomes in the GnomAD database, including 123 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.045 (119 hom., cov: 0)
  • Exomes 𝑓: 0.0052 (4 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.908

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS3	NM_000603.5	c.1752+142_1752+149del		intron_variant		ENST00000297494.8
NOS3	NM_001160109.2	c.1752+142_1752+149del		intron_variant
NOS3	NM_001160110.1	c.1752+142_1752+149del		intron_variant
NOS3	NM_001160111.1	c.1752+142_1752+149del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8	c.1752+142_1752+149del		intron_variant		1	NM_000603.5	P1

Frequencies

GnomAD3 genomes AF: 0.0449 AC: 2923 AN: 65102 Hom.: 120 Cov.: 0

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.0438

Gnomad AMR AF: 0.0499

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.0406

Gnomad SAS AF: 0.0495

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.0929

Gnomad NFE AF: 0.0523

Gnomad OTH AF: 0.0398

GnomAD4 exome AF: 0.00524 AC: 1078 AN: 205650 Hom.: 4 AF XY: 0.00548 AC XY: 624 AN XY: 113846

Gnomad4 AFR exome AF: 0.00278

Gnomad4 AMR exome AF: 0.00189

Gnomad4 ASJ exome AF: 0.00291

Gnomad4 EAS exome AF: 0.00454

Gnomad4 SAS exome AF: 0.00508

Gnomad4 FIN exome AF: 0.00601

Gnomad4 NFE exome AF: 0.00613

Gnomad4 OTH exome AF: 0.00632

GnomAD4 genome AF: 0.0449 AC: 2925 AN: 65162 Hom.: 119 Cov.: 0 AF XY: 0.0443 AC XY: 1329 AN XY: 30020

Gnomad4 AFR AF: 0.0335

Gnomad4 AMR AF: 0.0504

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.0403

Gnomad4 SAS AF: 0.0486

Gnomad4 FIN AF: 0.0403

Gnomad4 NFE AF: 0.0523

Gnomad4 OTH AF: 0.0405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3138808; hg19: chr7-150699471;