chr17-27768704-A-C

Variant names:

• chr17-27768704-A-C
• rs2297516
• NM_000625.4:c.2034+273T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000625.4(NOS2):​c.2034+273T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,116 control chromosomes in the GnomAD database, including 12,116 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 0.39 (12116 hom., cov: 33)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• Publications: 36 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.2034+273T>G		intron_variant	Intron 17 of 26	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.2034+273T>G		intron_variant	Intron 17 of 26	1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59993 AN: 151998 Hom.: 12089 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.420

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.395 AC: 60073 AN: 152116 Hom.: 12116 Cov.: 33 AF XY: 0.397 AC XY: 29504 AN XY: 74360

African (AFR) AF: 0.345 AC: 14314 AN: 41482

American (AMR) AF: 0.420 AC: 6422 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1462 AN: 3472

East Asian (EAS) AF: 0.530 AC: 2737 AN: 5166

South Asian (SAS) AF: 0.615 AC: 2969 AN: 4828

European-Finnish (FIN) AF: 0.340 AC: 3597 AN: 10584

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27254 AN: 67974

Other (OTH) AF: 0.425 AC: 898 AN: 2114

Alfa AF: 0.397 Hom.: 52238

Bravo AF: 0.391

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.67
PhyloP100		0.32
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: rs2297516; hg19: chr17-26095730;