Genetic Variant NM_000603.5:c.1752+122_1752+149delACACACACACACACACACACACACACAC (chr7-151002383-AACACACACACACACACACACACACACAC-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000603.5(NOS3):c.1752+122_1752+149delACACACACACACACACACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00334 in 270,948 control chromosomes in the GnomAD database, including 4 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_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 0.0048 ( 2 hom., cov: 0)

Exomes 𝑓: 0.0029 ( 2 hom. )

Consequence

NOS3
NM_000603.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.908

Publications

9 publications found

Variant links:

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]

NOS3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 315 AD gene.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NOS3	NM_000603.5	MANE Select	c.1752+122_1752+149delACACACACACACACACACACACACACAC	intron	N/A	NP_000594.2
NOS3	NM_001160111.1		c.1752+122_1752+149delACACACACACACACACACACACACACAC	intron	N/A	NP_001153583.1	P29474-2
NOS3	NM_001160110.1		c.1752+122_1752+149delACACACACACACACACACACACACACAC	intron	N/A	NP_001153582.1	P29474-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NOS3	ENST00000297494.8	TSL:1 MANE Select	c.1752+80_1752+107delACACACACACACACACACACACACACAC	intron	N/A	ENSP00000297494.3	P29474-1
NOS3	ENST00000484524.5	TSL:1	c.1752+80_1752+107delACACACACACACACACACACACACACAC	intron	N/A	ENSP00000420215.1	P29474-2
NOS3	ENST00000467517.1	TSL:1	c.1752+80_1752+107delACACACACACACACACACACACACACAC	intron	N/A	ENSP00000420551.1	P29474-3

Frequencies

GnomAD3 genomes

AF:

0.00474

AC:

309

AN:

65214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00721

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.000499

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.00190

Gnomad FIN

AF:

0.00828

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00382

Gnomad OTH

AF:

0.00233

GnomAD4 exome

AF:

0.00286

AC:

589

AN:

205676

Hom.:

AF XY:

0.00283

AC XY:

322

AN XY:

113860

show subpopulations

African (AFR)

AF:

0.00483

AC:

AN:

6828

American (AMR)

AF:

0.00100

AC:

AN:

19008

Ashkenazi Jewish (ASJ)

AF:

0.00277

AC:

AN:

6862

East Asian (EAS)

AF:

0.00468

AC:

AN:

7482

South Asian (SAS)

AF:

0.00360

AC:

139

AN:

38566

European-Finnish (FIN)

AF:

0.00316

AC:

AN:

9818

Middle Eastern (MID)

AF:

0.00238

AC:

AN:

842

European-Non Finnish (NFE)

AF:

0.00270

AC:

287

AN:

106130

Other (OTH)

AF:

0.00237

AC:

AN:

10140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.409

Heterozygous variant carriers

105

131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00483

AC:

315

AN:

65272

Hom.:

Cov.:

AF XY:

0.00509

AC XY:

153

AN XY:

30076

show subpopulations

African (AFR)

AF:

0.00746

AC:

132

AN:

17690

American (AMR)

AF:

0.00484

AC:

AN:

5584

Ashkenazi Jewish (ASJ)

AF:

0.000499

AC:

AN:

2006

East Asian (EAS)

AF:

0.00173

AC:

AN:

2310

South Asian (SAS)

AF:

0.00192

AC:

AN:

1566

European-Finnish (FIN)

AF:

0.00828

AC:

AN:

2778

Middle Eastern (MID)

AF:

0.00

AC:

AN:

132

European-Non Finnish (NFE)

AF:

0.00386

AC:

123

AN:

31904

Other (OTH)

AF:

0.00230

AC:

AN:

868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.91

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over