7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACAC

Variant names:

• chr7-151002383-AACACACACACACACACACACACAC-A
• rs3138808
• NM_000603.5:c.1752+126_1752+149delACACACACACACACACACACACAC

Variant summary

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

The NM_000603.5(NOS3):​c.1752+126_1752+149delACACACACACACACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00532 in 270,876 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0050 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0054 (2 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 324 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1752+126_1752+149delACACACACACACACACACACACAC		intron_variant	Intron 14 of 26	ENST00000297494.8	NP_000594.2
NOS3	NM_001160111.1	c.1752+126_1752+149delACACACACACACACACACACACAC		intron_variant	Intron 13 of 13		NP_001153583.1
NOS3	NM_001160110.1	c.1752+126_1752+149delACACACACACACACACACACACAC		intron_variant	Intron 13 of 13		NP_001153582.1
NOS3	NM_001160109.2	c.1752+126_1752+149delACACACACACACACACACACACAC		intron_variant	Intron 13 of 13		NP_001153581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.1752+80_1752+103delACACACACACACACACACACACAC		intron_variant	Intron 14 of 26	1	NM_000603.5	ENSP00000297494.3

Frequencies

GnomAD3 genomes AF: 0.00498 AC: 325 AN: 65210 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00732

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00269

Gnomad ASJ AF: 0.0204

Gnomad EAS AF: 0.00993

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.00108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00241

Gnomad OTH AF: 0.00816

GnomAD4 exome AF: 0.00543 AC: 1116 AN: 205608 Hom.: 2 AF XY: 0.00546 AC XY: 622 AN XY: 113818

Gnomad4 AFR exome AF: 0.00644

Gnomad4 AMR exome AF: 0.000842

Gnomad4 ASJ exome AF: 0.00904

Gnomad4 EAS exome AF: 0.0164

Gnomad4 SAS exome AF: 0.00713

Gnomad4 FIN exome AF: 0.00377

Gnomad4 NFE exome AF: 0.00465

Gnomad4 OTH exome AF: 0.00602

GnomAD4 genome AF: 0.00496 AC: 324 AN: 65268 Hom.: 2 Cov.: 0 AF XY: 0.00545 AC XY: 164 AN XY: 30072

Gnomad4 AFR AF: 0.00724

Gnomad4 AMR AF: 0.00269

Gnomad4 ASJ AF: 0.0204

Gnomad4 EAS AF: 0.00996

Gnomad4 SAS AF: 0.0192

Gnomad4 FIN AF: 0.00108

Gnomad4 NFE AF: 0.00241

Gnomad4 OTH AF: 0.00806

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;