7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACACACACACACACACACACACACACACACACACAC

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000603.5(NOS3):​c.1752+124_1752+149dupACACACACACACACACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 9 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000603.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	NM_000603.5	MANE Select	c.1752+124_1752+149dupACACACACACACACACACACACACAC		intron	N/A	NP_000594.2
	NOS3	NM_001160111.1		c.1752+124_1752+149dupACACACACACACACACACACACACAC		intron	N/A	NP_001153583.1	P29474-2
	NOS3	NM_001160110.1		c.1752+124_1752+149dupACACACACACACACACACACACACAC		intron	N/A	NP_001153582.1	P29474-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.1752+79_1752+80insACACACACACACACACACACACACAC		intron	N/A	ENSP00000297494.3	P29474-1
	NOS3	ENST00000484524.5	TSL:1	c.1752+79_1752+80insACACACACACACACACACACACACAC		intron	N/A	ENSP00000420215.1	P29474-2
	NOS3	ENST00000467517.1	TSL:1	c.1752+79_1752+80insACACACACACACACACACACACACAC		intron	N/A	ENSP00000420551.1	P29474-3

Frequencies

GnomAD3 genomes AF: 0.0000153 AC: 1 AN: 65212 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000313

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 205824 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 113952

African (AFR) AF: 0.00 AC: 0 AN: 6834

American (AMR) AF: 0.00 AC: 0 AN: 19016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6864

East Asian (EAS) AF: 0.00 AC: 0 AN: 7492

South Asian (SAS) AF: 0.00 AC: 0 AN: 38614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 842

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 106196

Other (OTH) AF: 0.00 AC: 0 AN: 10144

GnomAD4 genome AF: 0.0000153 AC: 1 AN: 65212 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 30002

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 17620

American (AMR) AF: 0.00 AC: 0 AN: 5574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2006

East Asian (EAS) AF: 0.00 AC: 0 AN: 2316

South Asian (SAS) AF: 0.00 AC: 0 AN: 1580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 140

European-Non Finnish (NFE) AF: 0.0000313 AC: 1 AN: 31906

Other (OTH) AF: 0.00 AC: 0 AN: 858

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.22

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3138808; hg19: chr7-150699471;