Genetic Variant NOS3:c.1752+142_1752+149dupACACACAC (chr7-151002383-A-AACACACAC) – 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+142_1752+149dupACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 271,072 control chromosomes in the GnomAD database, including 50 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0098 ( 40 hom., cov: 0)

Exomes 𝑓: 0.00051 ( 10 hom. )

Consequence

NOS3
NM_000603.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.222

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 642 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+142_1752+149dupACACACAC	intron	N/A	NP_000594.2
NOS3	NM_001160111.1		c.1752+142_1752+149dupACACACAC	intron	N/A	NP_001153583.1	P29474-2
NOS3	NM_001160110.1		c.1752+142_1752+149dupACACACAC	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+79_1752+80insACACACAC	intron	N/A	ENSP00000297494.3	P29474-1
NOS3	ENST00000484524.5	TSL:1	c.1752+79_1752+80insACACACAC	intron	N/A	ENSP00000420215.1	P29474-2
NOS3	ENST00000467517.1	TSL:1	c.1752+79_1752+80insACACACAC	intron	N/A	ENSP00000420551.1	P29474-3

Frequencies

GnomAD3 genomes

AF:

0.00983

AC:

641

AN:

65198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00726

Gnomad AMI

AF:

0.00922

Gnomad AMR

AF:

0.0149

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.00864

Gnomad SAS

AF:

0.00443

Gnomad FIN

AF:

0.00504

Gnomad MID

AF:

0.0214

Gnomad NFE

AF:

0.0110

Gnomad OTH

AF:

0.0105

GnomAD4 exome

AF:

0.000505

AC:

104

AN:

205816

Hom.:

AF XY:

0.000465

AC XY:

AN XY:

113946

show subpopulations

African (AFR)

AF:

0.000439

AC:

AN:

6834

American (AMR)

AF:

0.000210

AC:

AN:

19016

Ashkenazi Jewish (ASJ)

AF:

0.000146

AC:

AN:

6862

East Asian (EAS)

AF:

0.000401

AC:

AN:

7490

South Asian (SAS)

AF:

0.000596

AC:

AN:

38612

European-Finnish (FIN)

AF:

0.000305

AC:

AN:

9822

Middle Eastern (MID)

AF:

0.00119

AC:

AN:

842

European-Non Finnish (NFE)

AF:

0.000574

AC:

AN:

106194

Other (OTH)

AF:

0.000493

AC:

AN:

10144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.609

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00984

AC:

642

AN:

65256

Hom.:

Cov.:

AF XY:

0.00921

AC XY:

277

AN XY:

30066

show subpopulations

African (AFR)

AF:

0.00729

AC:

129

AN:

17688

American (AMR)

AF:

0.0149

AC:

AN:

5576

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

AN:

2006

East Asian (EAS)

AF:

0.00866

AC:

AN:

2310

South Asian (SAS)

AF:

0.00447

AC:

AN:

1566

European-Finnish (FIN)

AF:

0.00504

AC:

AN:

2778

Middle Eastern (MID)

AF:

0.0227

AC:

AN:

132

European-Non Finnish (NFE)

AF:

0.0110

AC:

351

AN:

31898

Other (OTH)

AF:

0.0104

AC:

AN:

868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.582

Heterozygous variant carriers

113

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

-0.22

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.

7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACACACACACACACACAC

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