rs3794756

Positions:

• chr17-27759603-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000625.4(NOS2):​c.3159+427G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 152,132 control chromosomes in the GnomAD database, including 275 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 0.041 (275 hom., cov: 33)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS2	NM_000625.4	c.3159+427G>A		intron_variant		ENST00000313735.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS2	ENST00000313735.11	c.3159+427G>A		intron_variant		1	NM_000625.4	P2

Frequencies

GnomAD3 genomes AF: 0.0405 AC: 6158 AN: 152014 Hom.: 272 Cov.: 33

Gnomad AFR AF: 0.0880

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.0516

Gnomad FIN AF: 0.0307

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00947

Gnomad OTH AF: 0.0269

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

GnomAD4 genome AF: 0.0405 AC: 6162 AN: 152132 Hom.: 275 Cov.: 33 AF XY: 0.0415 AC XY: 3085 AN XY: 74368

Gnomad4 AFR AF: 0.0879

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.00864

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.0508

Gnomad4 FIN AF: 0.0307

Gnomad4 NFE AF: 0.00948

Gnomad4 OTH AF: 0.0285

Alfa AF: 0.0148 Hom.: 43

Bravo AF: 0.0417

Asia WGS AF: 0.144 AC: 498 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	1.5
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3794756; hg19: chr17-26086629;