7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACAC

Variant names:

• chr7-151002383-AACACACACACACACACACACACACAC-A
• rs3138808
• NM_000603.5:c.1752+124_1752+149delACACACACACACACACACACACACAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000603.5(NOS3):​c.1752+124_1752+149delACACACACACACACACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00971 in 270,868 control chromosomes in the GnomAD database, including 30 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.022 (24 hom., cov: 0)
  • Exomes 𝑓: 0.0057 (6 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.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0225 (1467/65266) while in subpopulation SAS AF= 0.053 (83/1566). AF 95% confidence interval is 0.0438. There are 24 homozygotes in gnomad4. There are 707 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1467 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1752+124_1752+149delACACACACACACACACACACACACAC		intron_variant	Intron 14 of 26	ENST00000297494.8	NP_000594.2
NOS3	NM_001160111.1	c.1752+124_1752+149delACACACACACACACACACACACACAC		intron_variant	Intron 13 of 13		NP_001153583.1
NOS3	NM_001160110.1	c.1752+124_1752+149delACACACACACACACACACACACACAC		intron_variant	Intron 13 of 13		NP_001153582.1
NOS3	NM_001160109.2	c.1752+124_1752+149delACACACACACACACACACACACACAC		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+105delACACACACACACACACACACACACAC		intron_variant	Intron 14 of 26	1	NM_000603.5	ENSP00000297494.3

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 1466 AN: 65208 Hom.: 24 Cov.: 0

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.0115

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.00820

Gnomad SAS AF: 0.0525

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.00566 AC: 1163 AN: 205602 Hom.: 6 AF XY: 0.00603 AC XY: 686 AN XY: 113828

Gnomad4 AFR exome AF: 0.00674

Gnomad4 AMR exome AF: 0.000999

Gnomad4 ASJ exome AF: 0.00802

Gnomad4 EAS exome AF: 0.00828

Gnomad4 SAS exome AF: 0.00968

Gnomad4 FIN exome AF: 0.00336

Gnomad4 NFE exome AF: 0.00495

Gnomad4 OTH exome AF: 0.00484

GnomAD4 genome AF: 0.0225 AC: 1467 AN: 65266 Hom.: 24 Cov.: 0 AF XY: 0.0235 AC XY: 707 AN XY: 30072

Gnomad4 AFR AF: 0.0360

Gnomad4 AMR AF: 0.0154

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.00779

Gnomad4 SAS AF: 0.0530

Gnomad4 FIN AF: 0.0108

Gnomad4 NFE AF: 0.0166

Gnomad4 OTH AF: 0.0161

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;