rs2314812

Variant names:

• chr17-27783788-C-T
• rs2314812
• NM_000625.4:c.468-682G>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.468-682G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,274 control chromosomes in the GnomAD database, including 2,274 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 0.17 (2274 hom., cov: 33)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.468-682G>A		intron_variant	Intron 5 of 26	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.468-682G>A		intron_variant	Intron 5 of 26	1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25682 AN: 152156 Hom.: 2274 Cov.: 33

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0668

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.169 AC: 25693 AN: 152274 Hom.: 2274 Cov.: 33 AF XY: 0.168 AC XY: 12507 AN XY: 74444

African (AFR) AF: 0.180 AC: 7495 AN: 41544

American (AMR) AF: 0.132 AC: 2015 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 816 AN: 3472

East Asian (EAS) AF: 0.0668 AC: 346 AN: 5182

South Asian (SAS) AF: 0.142 AC: 686 AN: 4826

European-Finnish (FIN) AF: 0.183 AC: 1945 AN: 10606

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11645 AN: 68020

Other (OTH) AF: 0.182 AC: 385 AN: 2114

Alfa AF: 0.170 Hom.: 3753

Bravo AF: 0.168

Asia WGS AF: 0.0930 AC: 323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.25
DANN	Benign	0.48
PhyloP100		-1.6
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: rs2314812; hg19: chr17-26110814; COSMIC: COSV58224961;