7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACACACAC

Position:

• chr7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACACACAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000603.5(NOS3):​c.1752+148_1752+149delAC 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 270,808 control chromosomes in the GnomAD database, including 95 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.045 (95 hom., cov: 0)
  • Exomes 𝑓: 0.0015 (0 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.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1752+148_1752+149delAC		intron_variant		ENST00000297494.8	NP_000594.2
NOS3	NM_001160111.1	c.1752+148_1752+149delAC		intron_variant			NP_001153583.1
NOS3	NM_001160110.1	c.1752+148_1752+149delAC		intron_variant			NP_001153582.1
NOS3	NM_001160109.2	c.1752+148_1752+149delAC		intron_variant			NP_001153581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.1752+80_1752+81delAC		intron_variant		1	NM_000603.5	ENSP00000297494.3

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 2940 AN: 65038 Hom.: 95 Cov.: 0

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.0161

Gnomad AMR AF: 0.0692

Gnomad ASJ AF: 0.0325

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.0361

Gnomad MID AF: 0.0357

Gnomad NFE AF: 0.0544

Gnomad OTH AF: 0.0505

GnomAD4 exome AF: 0.00153 AC: 314 AN: 205714 Hom.: 0 AF XY: 0.00160 AC XY: 182 AN XY: 113892

Gnomad4 AFR exome AF: 0.000878

Gnomad4 AMR exome AF: 0.000578

Gnomad4 ASJ exome AF: 0.000437

Gnomad4 EAS exome AF: 0.00200

Gnomad4 SAS exome AF: 0.000699

Gnomad4 FIN exome AF: 0.00285

Gnomad4 NFE exome AF: 0.00198

Gnomad4 OTH exome AF: 0.00118

GnomAD4 genome AF: 0.0452 AC: 2941 AN: 65094 Hom.: 95 Cov.: 0 AF XY: 0.0447 AC XY: 1341 AN XY: 30006

Gnomad4 AFR AF: 0.0263

Gnomad4 AMR AF: 0.0691

Gnomad4 ASJ AF: 0.0325

Gnomad4 EAS AF: 0.0403

Gnomad4 SAS AF: 0.0321

Gnomad4 FIN AF: 0.0361

Gnomad4 NFE AF: 0.0544

Gnomad4 OTH AF: 0.0499

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;