7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACACACACACACACACAC

Position:

• chr7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACACACACACACACACAC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000297494.8(NOS3):​c.1752+142_1752+149dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 271,072 control chromosomes in the GnomAD database, including 50 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0098 (40 hom., cov: 0)
  • Exomes 𝑓: 0.00051 (10 hom.)
• Consequence: NOS3 ENST00000297494.8 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 642 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1752+142_1752+149dup		intron_variant		ENST00000297494.8	NP_000594.2
NOS3	NM_001160109.2	c.1752+142_1752+149dup		intron_variant			NP_001153581.1
NOS3	NM_001160110.1	c.1752+142_1752+149dup		intron_variant			NP_001153582.1
NOS3	NM_001160111.1	c.1752+142_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+142_1752+149dup		intron_variant		1	NM_000603.5	ENSP00000297494	P1

Frequencies

GnomAD3 genomes AF: 0.00983 AC: 641 AN: 65198 Hom.: 40 Cov.: 0

Gnomad AFR AF: 0.00726

Gnomad AMI AF: 0.00922

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.00864

Gnomad SAS AF: 0.00443

Gnomad FIN AF: 0.00504

Gnomad MID AF: 0.0214

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.000505 AC: 104 AN: 205816 Hom.: 10 AF XY: 0.000465 AC XY: 53 AN XY: 113946

Gnomad4 AFR exome AF: 0.000439

Gnomad4 AMR exome AF: 0.000210

Gnomad4 ASJ exome AF: 0.000146

Gnomad4 EAS exome AF: 0.000401

Gnomad4 SAS exome AF: 0.000596

Gnomad4 FIN exome AF: 0.000305

Gnomad4 NFE exome AF: 0.000574

Gnomad4 OTH exome AF: 0.000493

GnomAD4 genome AF: 0.00984 AC: 642 AN: 65256 Hom.: 40 Cov.: 0 AF XY: 0.00921 AC XY: 277 AN XY: 30066

Gnomad4 AFR AF: 0.00729

Gnomad4 AMR AF: 0.0149

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.00866

Gnomad4 SAS AF: 0.00447

Gnomad4 FIN AF: 0.00504

Gnomad4 NFE AF: 0.0110

Gnomad4 OTH AF: 0.0104

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;