rs4795067

Variant names:

• chr17-27779649-A-G
• rs4795067
• NM_000625.4:c.1005-593T>C

Variant summary

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

The NM_000625.4(NOS2):​c.1005-593T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,120 control chromosomes in the GnomAD database, including 7,640 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 0.31 (7640 hom., cov: 31)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278
• Publications: 75 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.1005-593T>C		intron_variant	Intron 9 of 26	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.1005-593T>C		intron_variant	Intron 9 of 26	1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47133 AN: 152002 Hom.: 7629 Cov.: 31

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.310 AC: 47165 AN: 152120 Hom.: 7640 Cov.: 31 AF XY: 0.313 AC XY: 23291 AN XY: 74346

African (AFR) AF: 0.217 AC: 8999 AN: 41510

American (AMR) AF: 0.305 AC: 4661 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1222 AN: 3470

East Asian (EAS) AF: 0.234 AC: 1209 AN: 5174

South Asian (SAS) AF: 0.413 AC: 1994 AN: 4824

European-Finnish (FIN) AF: 0.372 AC: 3925 AN: 10560

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23941 AN: 67984

Other (OTH) AF: 0.312 AC: 659 AN: 2110

Alfa AF: 0.338 Hom.: 42064

Bravo AF: 0.301

Asia WGS AF: 0.304 AC: 1055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.45
PhyloP100		0.28
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: rs4795067; hg19: chr17-26106675;