7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACACAC

Position:

• chr7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACACAC

Variant summary

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

The NM_000603.5(NOS3):​c.1752+146_1752+149del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 270,660 control chromosomes in the GnomAD database, including 149 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.055 (148 hom., cov: 0)
  • Exomes 𝑓: 0.0030 (1 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222

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 (AMR) allele frequency at 95% confidence interval = 0.0734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1752+146_1752+149del		intron_variant		ENST00000297494.8	NP_000594.2
NOS3	NM_001160109.2	c.1752+146_1752+149del		intron_variant			NP_001153581.1
NOS3	NM_001160110.1	c.1752+146_1752+149del		intron_variant			NP_001153582.1
NOS3	NM_001160111.1	c.1752+146_1752+149del		intron_variant			NP_001153583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.1752+146_1752+149del		intron_variant		1	NM_000603.5	ENSP00000297494	P1

Frequencies

GnomAD3 genomes AF: 0.0551 AC: 3583 AN: 64980 Hom.: 148 Cov.: 0

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.0276

Gnomad AMR AF: 0.0795

Gnomad ASJ AF: 0.0531

Gnomad EAS AF: 0.0468

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.0630

Gnomad MID AF: 0.0857

Gnomad NFE AF: 0.0626

Gnomad OTH AF: 0.0526

GnomAD4 exome AF: 0.00300 AC: 617 AN: 205620 Hom.: 1 AF XY: 0.00312 AC XY: 355 AN XY: 113848

Gnomad4 AFR exome AF: 0.00103

Gnomad4 AMR exome AF: 0.000789

Gnomad4 ASJ exome AF: 0.00233

Gnomad4 EAS exome AF: 0.00334

Gnomad4 SAS exome AF: 0.00283

Gnomad4 FIN exome AF: 0.00408

Gnomad4 NFE exome AF: 0.00358

Gnomad4 OTH exome AF: 0.00227

GnomAD4 genome AF: 0.0551 AC: 3582 AN: 65040 Hom.: 148 Cov.: 0 AF XY: 0.0562 AC XY: 1683 AN XY: 29962

Gnomad4 AFR AF: 0.0353

Gnomad4 AMR AF: 0.0796

Gnomad4 ASJ AF: 0.0531

Gnomad4 EAS AF: 0.0460

Gnomad4 SAS AF: 0.0457

Gnomad4 FIN AF: 0.0630

Gnomad4 NFE AF: 0.0626

Gnomad4 OTH AF: 0.0520

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3138808; hg19: chr7-150699471;