rs1113283

Positions:

• chr17-27780372-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.1004+395G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,146 control chromosomes in the GnomAD database, including 3,648 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 0.22 (3648 hom., cov: 33)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.846

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS2	NM_000625.4	c.1004+395G>A		intron_variant		ENST00000313735.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS2	ENST00000313735.11	c.1004+395G>A		intron_variant		1	NM_000625.4	P2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32724 AN: 152028 Hom.: 3647 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.215 AC: 32730 AN: 152146 Hom.: 3648 Cov.: 33 AF XY: 0.215 AC XY: 15993 AN XY: 74372

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.227

Alfa AF: 0.217 Hom.: 489

Bravo AF: 0.214

Asia WGS AF: 0.154 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.60

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: rs1113283; hg19: chr17-26107398;