Genetic Variant NOS2:p.Ala31Ala (chr17-27798717-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_000625.4(NOS2):c.93C>T(p.Ala31Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,612,452 control chromosomes in the GnomAD database, including 308 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 0.012 ( 33 hom., cov: 32)

Exomes 𝑓: 0.016 ( 275 hom. )

Consequence

NOS2
NM_000625.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.622

Publications

13 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:

ENSG00000266202 (HGNC:):

ENSG00000266202 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=-0.83).

BP7

Synonymous conserved (PhyloP=0.622 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0123 (1874/152290) while in subpopulation SAS AF = 0.0392 (189/4824). AF 95% confidence interval is 0.0346. There are 33 homozygotes in GnomAd4. There are 958 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 33 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4 link	c.93C>T	p.Ala31Ala	synonymous_variant	Exon 2 of 27	ENST00000313735.11	NP_000616.3	P35228-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOS2	ENST00000313735.11 link	c.93C>T	p.Ala31Ala	synonymous_variant	Exon 2 of 27	1	NM_000625.4	ENSP00000327251.6	P35228-1
NOS2	ENST00000697337.1 link	n.93C>T		non_coding_transcript_exon_variant	Exon 1 of 24			ENSP00000513259.1	A0A8V8TLB1
ENSG00000266202	ENST00000582441.1 link	c.*124C>T		downstream_gene_variant		4		ENSP00000462879.1	J3KTA2

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1872

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00290

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.00746

Gnomad ASJ

AF:

0.0366

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0387

Gnomad FIN

AF:

0.0146

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0162

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.0159

AC:

4002

AN:

251420

AF XY:

0.0177

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.00477

Gnomad ASJ exome

AF:

0.0369

Gnomad EAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.0147

Gnomad NFE exome

AF:

0.0160

Gnomad OTH exome

AF:

0.0140

GnomAD4 exome

AF:

0.0156

AC:

22775

AN:

1460162

Hom.:

275

Cov.:

AF XY:

0.0165

AC XY:

12022

AN XY:

726484

show subpopulations

African (AFR)

AF:

0.00141

AC:

AN:

33450

American (AMR)

AF:

0.00487

AC:

218

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0372

AC:

972

AN:

26114

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39682

South Asian (SAS)

AF:

0.0392

AC:

3380

AN:

86218

European-Finnish (FIN)

AF:

0.0156

AC:

832

AN:

53406

Middle Eastern (MID)

AF:

0.0236

AC:

136

AN:

5768

European-Non Finnish (NFE)

AF:

0.0146

AC:

16248

AN:

1110464

Other (OTH)

AF:

0.0156

AC:

940

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

1034

2068

3102

4136

5170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.0123

AC:

1874

AN:

152290

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

958

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00289

AC:

120

AN:

41560

American (AMR)

AF:

0.00745

AC:

114

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0366

AC:

127

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.0392

AC:

189

AN:

4824

European-Finnish (FIN)

AF:

0.0146

AC:

155

AN:

10612

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0162

AC:

1105

AN:

68032

Other (OTH)

AF:

0.0151

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

186

278

371

464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0143

Hom.:

Bravo

AF:

0.0100

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0193

EpiControl

AF:

0.0177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.9

(source)

DANN

Benign

0.49

PhyloP100

0.62

PromoterAI

-0.027

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over