rs2297516

Positions:

• chr17-27768704-A-C
• chr17-27768704-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NOS2	NM_000625.4	c.2034+273T>G		intron_variant		ENST00000313735.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS2	ENST00000313735.11	c.2034+273T>G		intron_variant		1	NM_000625.4	P2

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

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.425

Alfa AF: 0.400 Hom.: 25263

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

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

LitVar

Other links and lift over

dbSNP: rs2297516; hg19: chr17-26095730;