dbSNP rs16966563: NOS2:p.Pro68Pro (chr17-27788923-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000625.4(NOS2):c.204A>G(p.Pro68Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 1,613,798 control chromosomes in the GnomAD database, including 1,993 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.069 ( 811 hom., cov: 33)

Exomes 𝑓: 0.027 ( 1182 hom. )

Consequence

NOS2
NM_000625.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.225

Publications

16 publications found

Variant links:

Genes affected

NOS2 (HGNC:7873): (nitric oxide synthase 2) Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. This gene encodes a nitric oxide synthase which is expressed in liver and is inducible by a combination of lipopolysaccharide and certain cytokines. Three related pseudogenes are located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

NOS2 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

NOS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP7

Synonymous conserved (PhyloP=0.225 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4 link	c.204A>G	p.Pro68Pro	synonymous_variant	Exon 4 of 27	ENST00000313735.11	NP_000616.3	P35228-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11 link	c.204A>G	p.Pro68Pro	synonymous_variant	Exon 4 of 27	1	NM_000625.4	ENSP00000327251.6		P35228-1

Frequencies

GnomAD3 genomes

AF:

0.0693

AC:

10549

AN:

152152

Hom.:

810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0605

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.00734

Gnomad SAS

AF:

0.0478

Gnomad FIN

AF:

0.00536

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0194

Gnomad OTH

AF:

0.0463

GnomAD2 exomes

AF:

0.0372

AC:

9332

AN:

251182

AF XY:

0.0333

show subpopulations

Gnomad AFR exome

AF:

0.196

Gnomad AMR exome

AF:

0.0628

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.00979

Gnomad FIN exome

AF:

0.00508

Gnomad NFE exome

AF:

0.0179

Gnomad OTH exome

AF:

0.0276

GnomAD4 exome

AF:

0.0270

AC:

39398

AN:

1461528

Hom.:

1182

Cov.:

AF XY:

0.0268

AC XY:

19455

AN XY:

727024

show subpopulations

African (AFR)

AF:

0.193

AC:

6443

AN:

33466

American (AMR)

AF:

0.0628

AC:

2808

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0113

AC:

294

AN:

26118

East Asian (EAS)

AF:

0.00592

AC:

235

AN:

39688

South Asian (SAS)

AF:

0.0462

AC:

3979

AN:

86202

European-Finnish (FIN)

AF:

0.00543

AC:

290

AN:

53418

Middle Eastern (MID)

AF:

0.0266

AC:

153

AN:

5762

European-Non Finnish (NFE)

AF:

0.0208

AC:

23179

AN:

1111790

Other (OTH)

AF:

0.0334

AC:

2017

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1882

3764

5645

7527

9409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1042

2084

3126

4168

5210

<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:

0.0694

AC:

10567

AN:

152270

Hom.:

811

Cov.:

AF XY:

0.0680

AC XY:

5060

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.189

AC:

7835

AN:

41514

American (AMR)

AF:

0.0612

AC:

937

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

3470

East Asian (EAS)

AF:

0.00755

AC:

AN:

5166

South Asian (SAS)

AF:

0.0475

AC:

229

AN:

4824

European-Finnish (FIN)

AF:

0.00536

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0194

AC:

1317

AN:

68034

Other (OTH)

AF:

0.0458

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

458

916

1375

1833

2291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0369

Hom.:

480

Bravo

AF:

0.0783

Asia WGS

AF:

0.0360

AC:

124

AN:

3478

EpiCase

AF:

0.0173

EpiControl

AF:

0.0188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.1

(source)

DANN

Benign

0.66

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over