17-27768352-C-T

Variant names:

• chr17-27768352-C-T
• rs2314809
• NM_000625.4:c.2035-515G>A

Variant summary

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

The NM_000625.4(NOS2):​c.2035-515G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 152,002 control chromosomes in the GnomAD database, including 27,413 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 0.60 (27413 hom., cov: 32)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822
• Publications: 15 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.2035-515G>A		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.2035-515G>A		intron_variant	Intron 17 of 26	1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90789 AN: 151884 Hom.: 27369 Cov.: 32

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.598 AC: 90893 AN: 152002 Hom.: 27413 Cov.: 32 AF XY: 0.600 AC XY: 44584 AN XY: 74302

African (AFR) AF: 0.585 AC: 24222 AN: 41422

American (AMR) AF: 0.599 AC: 9156 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2348 AN: 3472

East Asian (EAS) AF: 0.680 AC: 3518 AN: 5172

South Asian (SAS) AF: 0.784 AC: 3771 AN: 4808

European-Finnish (FIN) AF: 0.527 AC: 5567 AN: 10560

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.589 AC: 40051 AN: 67966

Other (OTH) AF: 0.640 AC: 1351 AN: 2110

Alfa AF: 0.581 Hom.: 4364

Bravo AF: 0.596

Asia WGS AF: 0.736 AC: 2561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.57
DANN	Benign	0.25
PhyloP100		-0.82
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: rs2314809; hg19: chr17-26095378;