7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACACACACACACACACACAC

Position:

• chr7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACACACACACACACACACAC

Variant summary

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

The NM_000603.5(NOS3):​c.1752+140_1752+149dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 271,080 control chromosomes in the GnomAD database, including 19 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0049 (18 hom., cov: 0)
  • Exomes 𝑓: 0.00037 (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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 319 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1752+140_1752+149dup		intron_variant		ENST00000297494.8	NP_000594.2
NOS3	NM_001160109.2	c.1752+140_1752+149dup		intron_variant			NP_001153581.1
NOS3	NM_001160110.1	c.1752+140_1752+149dup		intron_variant			NP_001153582.1
NOS3	NM_001160111.1	c.1752+140_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+140_1752+149dup		intron_variant		1	NM_000603.5	ENSP00000297494	P1

Frequencies

GnomAD3 genomes AF: 0.00488 AC: 318 AN: 65206 Hom.: 18 Cov.: 0

Gnomad AFR AF: 0.00358

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00610

Gnomad ASJ AF: 0.00648

Gnomad EAS AF: 0.00345

Gnomad SAS AF: 0.00190

Gnomad FIN AF: 0.00108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00602

Gnomad OTH AF: 0.00233

GnomAD4 exome AF: 0.000369 AC: 76 AN: 205816 Hom.: 1 AF XY: 0.000325 AC XY: 37 AN XY: 113948

Gnomad4 AFR exome AF: 0.000293

Gnomad4 AMR exome AF: 0.000158

Gnomad4 ASJ exome AF: 0.000291

Gnomad4 EAS exome AF: 0.000667

Gnomad4 SAS exome AF: 0.000388

Gnomad4 FIN exome AF: 0.000611

Gnomad4 NFE exome AF: 0.000377

Gnomad4 OTH exome AF: 0.000296

GnomAD4 genome AF: 0.00489 AC: 319 AN: 65264 Hom.: 18 Cov.: 0 AF XY: 0.00416 AC XY: 125 AN XY: 30068

Gnomad4 AFR AF: 0.00362

Gnomad4 AMR AF: 0.00609

Gnomad4 ASJ AF: 0.00648

Gnomad4 EAS AF: 0.00346

Gnomad4 SAS AF: 0.00192

Gnomad4 FIN AF: 0.00108

Gnomad4 NFE AF: 0.00602

Gnomad4 OTH AF: 0.00230

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;