chr7-151002383-AACACACACACACACACACACACACACACACACACACAC-A

Variant names:

• chr7-151002383-AACACACACACACACACACACACACACACACACACACAC-A
• rs3138808
• NM_000603.5:c.1752+112_1752+149delACACACACACACACACACACACACACACACACACACAC

Variant summary

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

The NM_000603.5(NOS3):​c.1752+112_1752+149delACACACACACACACACACACACACACACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 271,082 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000061 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00015 (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 GnomAdExome4 at 31 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1752+112_1752+149delACACACACACACACACACACACACACACACACACACAC		intron_variant	Intron 14 of 26	ENST00000297494.8	NP_000594.2
NOS3	NM_001160111.1	c.1752+112_1752+149delACACACACACACACACACACACACACACACACACACAC		intron_variant	Intron 13 of 13		NP_001153583.1
NOS3	NM_001160110.1	c.1752+112_1752+149delACACACACACACACACACACACACACACACACACACAC		intron_variant	Intron 13 of 13		NP_001153582.1
NOS3	NM_001160109.2	c.1752+112_1752+149delACACACACACACACACACACACACACACACACACACAC		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+117delACACACACACACACACACACACACACACACACACACAC		intron_variant	Intron 14 of 26	1	NM_000603.5	ENSP00000297494.3

Frequencies

GnomAD3 genomes AF: 0.0000613 AC: 4 AN: 65212 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000568

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000359

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000432

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000151 AC: 31 AN: 205812 Hom.: 0 AF XY: 0.000132 AC XY: 15 AN XY: 113942

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00200

Gnomad4 SAS exome AF: 0.0000259

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000848

Gnomad4 OTH exome AF: 0.000591

GnomAD4 genome AF: 0.0000613 AC: 4 AN: 65270 Hom.: 0 Cov.: 0 AF XY: 0.0000333 AC XY: 1 AN XY: 30074

Gnomad4 AFR AF: 0.0000565

Gnomad4 AMR AF: 0.000358

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000433

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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;