Genetic Variant NOS3:c.1752+118_1752+149delACACACACACACACACACACACACACACACAC (chr7-151002383-AACACACACACACACACACACACACACACACAC-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_000603.5(NOS3):c.1752+118_1752+149delACACACACACACACACACACACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 271,048 control chromosomes in the GnomAD database, including 26 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 0.015 ( 23 hom., cov: 0)

Exomes 𝑓: 0.0010 ( 3 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: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.015 (981/65262) while in subpopulation AFR AF = 0.0519 (918/17680). AF 95% confidence interval is 0.0491. There are 23 homozygotes in GnomAd4. There are 495 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 981 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
NOS3	NM_000603.5	MANE Select	c.1752+118_1752+149delACACACACACACACACACACACACACACACAC	intron	N/A	NP_000594.2
NOS3	NM_001160111.1		c.1752+118_1752+149delACACACACACACACACACACACACACACACAC	intron	N/A	NP_001153583.1
NOS3	NM_001160110.1		c.1752+118_1752+149delACACACACACACACACACACACACACACACAC	intron	N/A	NP_001153582.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NOS3	ENST00000297494.8	TSL:1 MANE Select	c.1752+80_1752+111delACACACACACACACACACACACACACACACAC	intron	N/A	ENSP00000297494.3
NOS3	ENST00000484524.5	TSL:1	c.1752+80_1752+111delACACACACACACACACACACACACACACACAC	intron	N/A	ENSP00000420215.1
NOS3	ENST00000467517.1	TSL:1	c.1752+80_1752+111delACACACACACACACACACACACACACACACAC	intron	N/A	ENSP00000420551.1

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

985

AN:

65204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0524

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000864

Gnomad SAS

AF:

0.00190

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00714

Gnomad NFE

AF:

0.000282

Gnomad OTH

AF:

0.0152

GnomAD4 exome

AF:

0.00102

AC:

209

AN:

205786

Hom.:

AF XY:

0.000851

AC XY:

AN XY:

113938

show subpopulations

African (AFR)

AF:

0.0192

AC:

131

AN:

6818

American (AMR)

AF:

0.000684

AC:

AN:

19014

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6862

East Asian (EAS)

AF:

0.00134

AC:

AN:

7488

South Asian (SAS)

AF:

0.000207

AC:

AN:

38612

European-Finnish (FIN)

AF:

0.000204

AC:

AN:

9820

Middle Eastern (MID)

AF:

0.00

AC:

AN:

842

European-Non Finnish (NFE)

AF:

0.000226

AC:

AN:

106186

Other (OTH)

AF:

0.00207

AC:

AN:

10144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

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:

0.0150

AC:

981

AN:

65262

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

495

AN XY:

30070

show subpopulations

African (AFR)

AF:

0.0519

AC:

918

AN:

17680

American (AMR)

AF:

0.00627

AC:

AN:

5584

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2006

East Asian (EAS)

AF:

0.000866

AC:

AN:

2310

South Asian (SAS)

AF:

0.00192

AC:

AN:

1566

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2778

Middle Eastern (MID)

AF:

0.00758

AC:

AN:

132

European-Non Finnish (NFE)

AF:

0.000282

AC:

AN:

31904

Other (OTH)

AF:

0.0150

AC:

AN:

868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.593

Heterozygous variant carriers

130

163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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

=98/2

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