rs4795067

Positions:

• chr17-27779649-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NOS2	NM_000625.4	c.1005-593T>C		intron_variant		ENST00000313735.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS2	ENST00000313735.11	c.1005-593T>C		intron_variant		1	NM_000625.4	P2

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

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.312

Alfa AF: 0.343 Hom.: 20348

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4795067; hg19: chr17-26106675;