rs2779248

Variant names:

• chr17-27800806-T-C
• rs2779248
• ENST00000582441.1:c.439-1924A>G

Variant summary

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

The ENST00000582441.1(ENSG00000266202):​c.439-1924A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,956 control chromosomes in the GnomAD database, including 11,800 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 (11800 hom., cov: 31)
• Consequence: ENSG00000266202 ENST00000582441.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 40 publications found

Genes affected

ENSG00000266202 (HGNC:):

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000582441.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000266202	ENST00000582441.1	TSL:4	c.439-1924A>G		intron	N/A	ENSP00000462879.1	J3KTA2
	NOS2	ENST00000886820.1		c.-315A>G		upstream_gene	N/A	ENSP00000556879.1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58834 AN: 151838 Hom.: 11793 Cov.: 31

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.388 AC: 58888 AN: 151956 Hom.: 11800 Cov.: 31 AF XY: 0.382 AC XY: 28385 AN XY: 74278

African (AFR) AF: 0.445 AC: 18463 AN: 41460

American (AMR) AF: 0.347 AC: 5287 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1866 AN: 3470

East Asian (EAS) AF: 0.168 AC: 866 AN: 5164

South Asian (SAS) AF: 0.304 AC: 1462 AN: 4810

European-Finnish (FIN) AF: 0.328 AC: 3464 AN: 10546

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.382 AC: 25933 AN: 67934

Other (OTH) AF: 0.404 AC: 853 AN: 2114

Alfa AF: 0.389 Hom.: 31704

Bravo AF: 0.396

Asia WGS AF: 0.230 AC: 798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.044
DANN	Benign	0.56
PhyloP100		-1.6
PromoterAI		0.013	Neutral

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2779248;

hg19: chr17-26127832;