17-27784402-G-A

Variant names:

• chr17-27784402-G-A
• rs3794764
• NM_000625.4:c.468-1296C>T

Variant summary

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

The NM_000625.4(NOS2):​c.468-1296C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,044 control chromosomes in the GnomAD database, including 5,057 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 0.25 (5057 hom., cov: 32)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260
• Publications: 23 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000625.4. 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
	NOS2	NM_000625.4	MANE Select	c.468-1296C>T		intron	N/A	NP_000616.3	P35228-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS2	ENST00000313735.11	TSL:1 MANE Select	c.468-1296C>T		intron	N/A	ENSP00000327251.6	P35228-1
	NOS2	ENST00000886820.1		c.468-1296C>T		intron	N/A	ENSP00000556879.1
	NOS2	ENST00000646938.1		c.465-1296C>T		intron	N/A	ENSP00000494870.1	A0A2R8YDS4

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38383 AN: 151926 Hom.: 5053 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.253 AC: 38410 AN: 152044 Hom.: 5057 Cov.: 32 AF XY: 0.254 AC XY: 18873 AN XY: 74296

African (AFR) AF: 0.294 AC: 12195 AN: 41450

American (AMR) AF: 0.305 AC: 4653 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3470

East Asian (EAS) AF: 0.210 AC: 1081 AN: 5152

South Asian (SAS) AF: 0.275 AC: 1327 AN: 4818

European-Finnish (FIN) AF: 0.215 AC: 2277 AN: 10578

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15023 AN: 67982

Other (OTH) AF: 0.269 AC: 567 AN: 2108

Alfa AF: 0.225 Hom.: 16931

Bravo AF: 0.259

Asia WGS AF: 0.260 AC: 906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.56
PhyloP100		0.26
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: rs3794764; hg19: chr17-26111428;