7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACACACACACACACAC

Position:

• chr7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACACACACACACACAC

Variant summary

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

The NM_000603.5(NOS3):​c.1752+144_1752+149dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 271,030 control chromosomes in the GnomAD database, including 164 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.022 (129 hom., cov: 0)
  • Exomes 𝑓: 0.0011 (35 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.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0222 (1445/65214) while in subpopulation NFE AF= 0.0277 (884/31886). AF 95% confidence interval is 0.0262. There are 129 homozygotes in gnomad4. There are 675 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1445 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1752+144_1752+149dup		intron_variant		ENST00000297494.8	NP_000594.2
NOS3	NM_001160109.2	c.1752+144_1752+149dup		intron_variant			NP_001153581.1
NOS3	NM_001160110.1	c.1752+144_1752+149dup		intron_variant			NP_001153582.1
NOS3	NM_001160111.1	c.1752+144_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+144_1752+149dup		intron_variant		1	NM_000603.5	ENSP00000297494	P1

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 1445 AN: 65152 Hom.: 129 Cov.: 0

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.00691

Gnomad AMR AF: 0.0231

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.00888

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.0143

Gnomad NFE AF: 0.0277

Gnomad OTH AF: 0.0292

GnomAD4 exome AF: 0.00111 AC: 229 AN: 205816 Hom.: 35 AF XY: 0.00112 AC XY: 128 AN XY: 113946

Gnomad4 AFR exome AF: 0.00117

Gnomad4 AMR exome AF: 0.000210

Gnomad4 ASJ exome AF: 0.000437

Gnomad4 EAS exome AF: 0.00160

Gnomad4 SAS exome AF: 0.00114

Gnomad4 FIN exome AF: 0.000713

Gnomad4 NFE exome AF: 0.00130

Gnomad4 OTH exome AF: 0.000887

GnomAD4 genome AF: 0.0222 AC: 1445 AN: 65214 Hom.: 129 Cov.: 0 AF XY: 0.0225 AC XY: 675 AN XY: 30048

Gnomad4 AFR AF: 0.0152

Gnomad4 AMR AF: 0.0231

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.0156

Gnomad4 SAS AF: 0.00896

Gnomad4 FIN AF: 0.0166

Gnomad4 NFE AF: 0.0277

Gnomad4 OTH AF: 0.0289

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;