NM_000603.5:c.1752+132_1752+149delACACACACACACACACAC

Variant names:

• chr7-151002383-AACACACACACACACACAC-A
• rs3138808
• NM_000603.5:c.1752+132_1752+149delACACACACACACACACAC

Variant summary

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

The NM_000603.5(NOS3):​c.1752+132_1752+149delACACACACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 270,752 control chromosomes in the GnomAD database, including 149 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.055 (142 hom., cov: 0)
  • Exomes 𝑓: 0.0076 (7 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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1752+132_1752+149delACACACACACACACACAC		intron_variant	Intron 14 of 26	ENST00000297494.8	NP_000594.2
NOS3	NM_001160111.1	c.1752+132_1752+149delACACACACACACACACAC		intron_variant	Intron 13 of 13		NP_001153583.1
NOS3	NM_001160110.1	c.1752+132_1752+149delACACACACACACACACAC		intron_variant	Intron 13 of 13		NP_001153582.1
NOS3	NM_001160109.2	c.1752+132_1752+149delACACACACACACACACAC		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+97delACACACACACACACACAC		intron_variant	Intron 14 of 26	1	NM_000603.5	ENSP00000297494.3

Frequencies

GnomAD3 genomes AF: 0.0546 AC: 3561 AN: 65170 Hom.: 143 Cov.: 0

Gnomad AFR AF: 0.0995

Gnomad AMI AF: 0.0787

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.0307

Gnomad SAS AF: 0.0374

Gnomad FIN AF: 0.0274

Gnomad MID AF: 0.0714

Gnomad NFE AF: 0.0365

Gnomad OTH AF: 0.0443

GnomAD4 exome AF: 0.00762 AC: 1566 AN: 205524 Hom.: 7 AF XY: 0.00810 AC XY: 921 AN XY: 113754

Gnomad4 AFR exome AF: 0.0130

Gnomad4 AMR exome AF: 0.00184

Gnomad4 ASJ exome AF: 0.00876

Gnomad4 EAS exome AF: 0.0170

Gnomad4 SAS exome AF: 0.0117

Gnomad4 FIN exome AF: 0.00663

Gnomad4 NFE exome AF: 0.00633

Gnomad4 OTH exome AF: 0.00622

GnomAD4 genome AF: 0.0546 AC: 3562 AN: 65228 Hom.: 142 Cov.: 0 AF XY: 0.0538 AC XY: 1616 AN XY: 30054

Gnomad4 AFR AF: 0.0994

Gnomad4 AMR AF: 0.0331

Gnomad4 ASJ AF: 0.0862

Gnomad4 EAS AF: 0.0307

Gnomad4 SAS AF: 0.0384

Gnomad4 FIN AF: 0.0274

Gnomad4 NFE AF: 0.0364

Gnomad4 OTH AF: 0.0438

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;