7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACAC

Position:

• chr7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACAC

Variant summary

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

The NM_000603.5(NOS3):​c.1752+120_1752+149delACACACACACACACACACACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 271,058 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0034 (2 hom., cov: 0)
  • Exomes 𝑓: 0.00087 (0 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.908

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 219 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1752+120_1752+149delACACACACACACACACACACACACACACAC		intron_variant		ENST00000297494.8	NP_000594.2
NOS3	NM_001160111.1	c.1752+120_1752+149delACACACACACACACACACACACACACACAC		intron_variant			NP_001153583.1
NOS3	NM_001160110.1	c.1752+120_1752+149delACACACACACACACACACACACACACACAC		intron_variant			NP_001153582.1
NOS3	NM_001160109.2	c.1752+120_1752+149delACACACACACACACACACACACACACACAC		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+109delACACACACACACACACACACACACACACAC		intron_variant		1	NM_000603.5	ENSP00000297494.3

Frequencies

GnomAD3 genomes AF: 0.00337 AC: 220 AN: 65214 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00377

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000432

Gnomad SAS AF: 0.000633

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000407

Gnomad OTH AF: 0.00583

GnomAD4 exome AF: 0.000875 AC: 180 AN: 205786 Hom.: 0 AF XY: 0.000869 AC XY: 99 AN XY: 113932

Gnomad4 AFR exome AF: 0.00293

Gnomad4 AMR exome AF: 0.000526

Gnomad4 ASJ exome AF: 0.000583

Gnomad4 EAS exome AF: 0.00200

Gnomad4 SAS exome AF: 0.00101

Gnomad4 FIN exome AF: 0.00102

Gnomad4 NFE exome AF: 0.000706

Gnomad4 OTH exome AF: 0.000690

GnomAD4 genome AF: 0.00336 AC: 219 AN: 65272 Hom.: 2 Cov.: 0 AF XY: 0.00313 AC XY: 94 AN XY: 30076

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.00376

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000433

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000407

Gnomad4 OTH AF: 0.00576

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;