dbSNP rs3730013: NOS2:c.-73-10C>T (chr17-27798892-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000625.4(NOS2):c.-73-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 886,886 control chromosomes in the GnomAD database, including 53,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.34 ( 8780 hom., cov: 31)

Exomes 𝑓: 0.35 ( 44784 hom. )

Consequence

NOS2
NM_000625.4 intron

Scores

Splicing: ADA: 0.0001112

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.663

Publications

23 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 17-27798892-G-A is Benign according to our data. Variant chr17-27798892-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688120.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000625.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS2	NM_000625.4	MANE Select	c.-73-10C>T		intron	N/A	NP_000616.3	P35228-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NOS2	ENST00000313735.11	TSL:1 MANE Select	c.-73-10C>T	intron	N/A	ENSP00000327251.6	P35228-1
ENSG00000266202	ENST00000582441.1	TSL:4	c.439-10C>T	intron	N/A	ENSP00000462879.1	J3KTA2
NOS2	ENST00000886820.1		c.-73-10C>T	intron	N/A	ENSP00000556879.1

Frequencies

GnomAD3 genomes

AF:

0.336

AC:

51076

AN:

151856

Hom.:

8777

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.407

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.423

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.337

Gnomad OTH

AF:

0.329

GnomAD2 exomes

AF:

0.367

AC:

76702

AN:

209188

AF XY:

0.366

show subpopulations

Gnomad AFR exome

AF:

0.309

Gnomad AMR exome

AF:

0.480

Gnomad ASJ exome

AF:

0.361

Gnomad EAS exome

AF:

0.329

Gnomad FIN exome

AF:

0.334

Gnomad NFE exome

AF:

0.338

Gnomad OTH exome

AF:

0.358

GnomAD4 exome

AF:

0.348

AC:

255688

AN:

734912

Hom.:

44784

Cov.:

AF XY:

0.350

AC XY:

136515

AN XY:

390148

show subpopulations

African (AFR)

AF:

0.308

AC:

6101

AN:

19812

American (AMR)

AF:

0.470

AC:

18658

AN:

39680

Ashkenazi Jewish (ASJ)

AF:

0.358

AC:

7435

AN:

20758

East Asian (EAS)

AF:

0.354

AC:

12820

AN:

36228

South Asian (SAS)

AF:

0.408

AC:

28123

AN:

68858

European-Finnish (FIN)

AF:

0.329

AC:

16437

AN:

49984

Middle Eastern (MID)

AF:

0.404

AC:

1763

AN:

4366

European-Non Finnish (NFE)

AF:

0.331

AC:

151845

AN:

458622

Other (OTH)

AF:

0.342

AC:

12506

AN:

36604

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

9136

18271

27407

36542

45678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2618

5236

7854

10472

13090

<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:

0.336

AC:

51116

AN:

151974

Hom.:

8780

Cov.:

AF XY:

0.341

AC XY:

25320

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.305

AC:

12627

AN:

41418

American (AMR)

AF:

0.407

AC:

6213

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.353

AC:

1225

AN:

3470

East Asian (EAS)

AF:

0.315

AC:

1628

AN:

5170

South Asian (SAS)

AF:

0.424

AC:

2034

AN:

4800

European-Finnish (FIN)

AF:

0.324

AC:

3425

AN:

10562

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.337

AC:

22906

AN:

67962

Other (OTH)

AF:

0.330

AC:

697

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1711

3421

5132

6842

8553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.336

Hom.:

13239

Bravo

AF:

0.338

Asia WGS

AF:

0.374

AC:

1302

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.53

PhyloP100

0.66

PromoterAI

0.0053

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0060

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

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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