7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACACACACACAC

Position:

• chr7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACACACACACAC

Variant summary

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

The NM_000603.5(NOS3):​c.1752+148_1752+149dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 270,932 control chromosomes in the GnomAD database, including 301 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.051 (273 hom., cov: 0)
  • Exomes 𝑓: 0.0013 (28 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 = 0.0567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1752+148_1752+149dup		intron_variant		ENST00000297494.8	NP_000594.2
NOS3	NM_001160109.2	c.1752+148_1752+149dup		intron_variant			NP_001153581.1
NOS3	NM_001160110.1	c.1752+148_1752+149dup		intron_variant			NP_001153582.1
NOS3	NM_001160111.1	c.1752+148_1752+149dup		intron_variant			NP_001153583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.1752+148_1752+149dup		intron_variant		1	NM_000603.5	ENSP00000297494	P1

Frequencies

GnomAD3 genomes AF: 0.0511 AC: 3326 AN: 65098 Hom.: 273 Cov.: 0

Gnomad AFR AF: 0.0372

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0611

Gnomad ASJ AF: 0.0459

Gnomad EAS AF: 0.0537

Gnomad SAS AF: 0.0305

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.0357

Gnomad NFE AF: 0.0590

Gnomad OTH AF: 0.0434

GnomAD4 exome AF: 0.00128 AC: 264 AN: 205774 Hom.: 28 AF XY: 0.00129 AC XY: 147 AN XY: 113920

Gnomad4 AFR exome AF: 0.000878

Gnomad4 AMR exome AF: 0.000263

Gnomad4 ASJ exome AF: 0.000437

Gnomad4 EAS exome AF: 0.00200

Gnomad4 SAS exome AF: 0.000855

Gnomad4 FIN exome AF: 0.00194

Gnomad4 NFE exome AF: 0.00161

Gnomad4 OTH exome AF: 0.00118

GnomAD4 genome AF: 0.0511 AC: 3327 AN: 65158 Hom.: 273 Cov.: 0 AF XY: 0.0514 AC XY: 1542 AN XY: 30020

Gnomad4 AFR AF: 0.0371

Gnomad4 AMR AF: 0.0610

Gnomad4 ASJ AF: 0.0459

Gnomad4 EAS AF: 0.0539

Gnomad4 SAS AF: 0.0307

Gnomad4 FIN AF: 0.0466

Gnomad4 NFE AF: 0.0590

Gnomad4 OTH AF: 0.0429

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;