7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACACACACACACAC

Position:

• chr7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACACACACACACAC

Variant summary

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

The NM_000603.5(NOS3):​c.1752+146_1752+149dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00977 in 270,980 control chromosomes in the GnomAD database, including 235 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.037 (197 hom., cov: 0)
  • Exomes 𝑓: 0.0011 (38 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 = 0.037 (2412/65198) while in subpopulation NFE AF= 0.0447 (1424/31892). AF 95% confidence interval is 0.0427. There are 197 homozygotes in gnomad4. There are 1082 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2412 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1752+146_1752+149dup		intron_variant		ENST00000297494.8	NP_000594.2
NOS3	NM_001160109.2	c.1752+146_1752+149dup		intron_variant			NP_001153581.1
NOS3	NM_001160110.1	c.1752+146_1752+149dup		intron_variant			NP_001153582.1
NOS3	NM_001160111.1	c.1752+146_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+146_1752+149dup		intron_variant		1	NM_000603.5	ENSP00000297494	P1

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 2414 AN: 65140 Hom.: 197 Cov.: 0

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0446

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.0372

Gnomad SAS AF: 0.0165

Gnomad FIN AF: 0.0400

Gnomad MID AF: 0.0429

Gnomad NFE AF: 0.0446

Gnomad OTH AF: 0.0386

GnomAD4 exome AF: 0.00115 AC: 236 AN: 205782 Hom.: 38 AF XY: 0.00114 AC XY: 130 AN XY: 113928

Gnomad4 AFR exome AF: 0.00117

Gnomad4 AMR exome AF: 0.000210

Gnomad4 ASJ exome AF: 0.000874

Gnomad4 EAS exome AF: 0.000668

Gnomad4 SAS exome AF: 0.00122

Gnomad4 FIN exome AF: 0.00194

Gnomad4 NFE exome AF: 0.00127

Gnomad4 OTH exome AF: 0.00109

GnomAD4 genome AF: 0.0370 AC: 2412 AN: 65198 Hom.: 197 Cov.: 0 AF XY: 0.0360 AC XY: 1082 AN XY: 30028

Gnomad4 AFR AF: 0.0241

Gnomad4 AMR AF: 0.0445

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.0369

Gnomad4 SAS AF: 0.0160

Gnomad4 FIN AF: 0.0400

Gnomad4 NFE AF: 0.0447

Gnomad4 OTH AF: 0.0381

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;