rs1137933

Variant names:

• chr17-27778906-G-A
• rs1137933
• NM_000625.4:c.1155C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-27778906-G-A
• chr17-27778906-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000625.4(NOS2):​c.1155C>T​(p.Asp385Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,606,554 control chromosomes in the GnomAD database, including 38,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3380 hom., cov: 31)
  • Exomes 𝑓: 0.22 (34832 hom.)
• Consequence: NOS2 NM_000625.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.631
• Publications: 64 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 17-27778906-G-A is Benign according to our data. Variant chr17-27778906-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688251.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.631 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.1155C>T	p.Asp385Asp	synonymous_variant	Exon 10 of 27	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.1155C>T	p.Asp385Asp	synonymous_variant	Exon 10 of 27	1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31426 AN: 151852 Hom.: 3380 Cov.: 31

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.227

GnomAD2 exomes AF: 0.205 AC: 50930 AN: 248726 AF XY: 0.209

Gnomad AFR exome AF: 0.179

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.168

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.225

GnomAD4 exome AF: 0.216 AC: 314117 AN: 1454584 Hom.: 34832 Cov.: 34 AF XY: 0.216 AC XY: 156003 AN XY: 722268

African (AFR) AF: 0.179 AC: 5955 AN: 33300

American (AMR) AF: 0.145 AC: 6439 AN: 44292

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 7055 AN: 25942

East Asian (EAS) AF: 0.117 AC: 4632 AN: 39528

South Asian (SAS) AF: 0.192 AC: 16491 AN: 85824

European-Finnish (FIN) AF: 0.208 AC: 11102 AN: 53326

Middle Eastern (MID) AF: 0.236 AC: 1355 AN: 5738

European-Non Finnish (NFE) AF: 0.224 AC: 248349 AN: 1106632

Other (OTH) AF: 0.212 AC: 12739 AN: 60002

GnomAD4 genome AF: 0.207 AC: 31432 AN: 151970 Hom.: 3380 Cov.: 31 AF XY: 0.207 AC XY: 15353 AN XY: 74260

African (AFR) AF: 0.179 AC: 7401 AN: 41426

American (AMR) AF: 0.189 AC: 2888 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 947 AN: 3466

East Asian (EAS) AF: 0.166 AC: 856 AN: 5160

South Asian (SAS) AF: 0.188 AC: 900 AN: 4796

European-Finnish (FIN) AF: 0.216 AC: 2284 AN: 10556

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15211 AN: 67974

Other (OTH) AF: 0.224 AC: 472 AN: 2110

Alfa AF: 0.201 Hom.: 2110

Bravo AF: 0.206

Asia WGS AF: 0.152 AC: 527 AN: 3478

EpiCase AF: 0.231

EpiControl AF: 0.225

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 29% of patients studied by a panel of primary immunodeficiencies. Number of patients: 28. Only high quality variants are reported. -

NOS2-related disorder Benign:1

Oct 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.9
DANN	Benign	0.35
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1137933; hg19: chr17-26105932; COSMIC: COSV58222552;