Genetic Variant NM_000603.5:c.1752+140_1752+149dupACACACACAC (chr7-151002383-A-AACACACACAC) – 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+140_1752+149dupACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 271,080 control chromosomes in the GnomAD database, including 19 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0049 ( 18 hom., cov: 0)

Exomes 𝑓: 0.00037 ( 1 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:

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ACMG classification

Classification was made for transcript

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

BS2

High AC in GnomAd4 at 319 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+140_1752+149dupACACACACAC	intron	N/A	NP_000594.2
NOS3	NM_001160111.1		c.1752+140_1752+149dupACACACACAC	intron	N/A	NP_001153583.1	P29474-2
NOS3	NM_001160110.1		c.1752+140_1752+149dupACACACACAC	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+80insACACACACAC	intron	N/A	ENSP00000297494.3	P29474-1
NOS3	ENST00000484524.5	TSL:1	c.1752+79_1752+80insACACACACAC	intron	N/A	ENSP00000420215.1	P29474-2
NOS3	ENST00000467517.1	TSL:1	c.1752+79_1752+80insACACACACAC	intron	N/A	ENSP00000420551.1	P29474-3

Frequencies

GnomAD3 genomes

AF:

0.00488

AC:

318

AN:

65206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00358

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00610

Gnomad ASJ

AF:

0.00648

Gnomad EAS

AF:

0.00345

Gnomad SAS

AF:

0.00190

Gnomad FIN

AF:

0.00108

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00602

Gnomad OTH

AF:

0.00233

GnomAD4 exome

AF:

0.000369

AC:

AN:

205816

Hom.:

AF XY:

0.000325

AC XY:

AN XY:

113948

show subpopulations

African (AFR)

AF:

0.000293

AC:

AN:

6834

American (AMR)

AF:

0.000158

AC:

AN:

19014

Ashkenazi Jewish (ASJ)

AF:

0.000291

AC:

AN:

6864

East Asian (EAS)

AF:

0.000667

AC:

AN:

7492

South Asian (SAS)

AF:

0.000388

AC:

AN:

38614

European-Finnish (FIN)

AF:

0.000611

AC:

AN:

9822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

842

European-Non Finnish (NFE)

AF:

0.000377

AC:

AN:

106190

Other (OTH)

AF:

0.000296

AC:

AN:

10144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

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:

0.00489

AC:

319

AN:

65264

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

125

AN XY:

30068

show subpopulations

African (AFR)

AF:

0.00362

AC:

AN:

17686

American (AMR)

AF:

0.00609

AC:

AN:

5584

Ashkenazi Jewish (ASJ)

AF:

0.00648

AC:

AN:

2006

East Asian (EAS)

AF:

0.00346

AC:

AN:

2310

South Asian (SAS)

AF:

0.00192

AC:

AN:

1566

European-Finnish (FIN)

AF:

0.00108

AC:

AN:

2776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

132

European-Non Finnish (NFE)

AF:

0.00602

AC:

192

AN:

31902

Other (OTH)

AF:

0.00230

AC:

AN:

868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.583

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

-0.22

Splicing

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

Publications

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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