7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACAC

Position:

• chr7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000297494.8(NOS3):​c.1752+136_1752+149del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 270,760 control chromosomes in the GnomAD database, including 48 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.027 (46 hom., cov: 0)
  • Exomes 𝑓: 0.0071 (2 hom.)
• Consequence: NOS3 ENST00000297494.8 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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0273 (1783/65236) while in subpopulation AFR AF= 0.0424 (750/17670). AF 95% confidence interval is 0.0399. There are 46 homozygotes in gnomad4. There are 812 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1783 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1752+136_1752+149del		intron_variant		ENST00000297494.8	NP_000594.2
NOS3	NM_001160109.2	c.1752+136_1752+149del		intron_variant			NP_001153581.1
NOS3	NM_001160110.1	c.1752+136_1752+149del		intron_variant			NP_001153582.1
NOS3	NM_001160111.1	c.1752+136_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+136_1752+149del		intron_variant		1	NM_000603.5	ENSP00000297494	P1

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 1780 AN: 65178 Hom.: 45 Cov.: 0

Gnomad AFR AF: 0.0423

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.0389

Gnomad SAS AF: 0.0399

Gnomad FIN AF: 0.0390

Gnomad MID AF: 0.0286

Gnomad NFE AF: 0.0176

Gnomad OTH AF: 0.0396

GnomAD4 exome AF: 0.00708 AC: 1456 AN: 205524 Hom.: 2 AF XY: 0.00731 AC XY: 832 AN XY: 113770

Gnomad4 AFR exome AF: 0.00571

Gnomad4 AMR exome AF: 0.00231

Gnomad4 ASJ exome AF: 0.00627

Gnomad4 EAS exome AF: 0.00655

Gnomad4 SAS exome AF: 0.0103

Gnomad4 FIN exome AF: 0.0102

Gnomad4 NFE exome AF: 0.00674

Gnomad4 OTH exome AF: 0.00592

GnomAD4 genome AF: 0.0273 AC: 1783 AN: 65236 Hom.: 46 Cov.: 0 AF XY: 0.0270 AC XY: 812 AN XY: 30056

Gnomad4 AFR AF: 0.0424

Gnomad4 AMR AF: 0.0199

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.0390

Gnomad4 SAS AF: 0.0383

Gnomad4 FIN AF: 0.0390

Gnomad4 NFE AF: 0.0176

Gnomad4 OTH AF: 0.0403

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;