rs2072324

chr17-27789870-C-Achr17-27789870-C-G

Variant summary

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

The NM_000625.4(NOS2):c.111-182G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,170 control chromosomes in the GnomAD database, including 2,973 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 0.19 (2973 hom., cov: 32)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289

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 (AMR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS2	NM_000625.4	c.111-182G>T		intron_variant		ENST00000313735.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS2	ENST00000313735.11	c.111-182G>T		intron_variant		1	NM_000625.4	P2

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28777 AN: 152052 Hom.: 2967 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.189 AC: 28792 AN: 152170 Hom.: 2973 Cov.: 32 AF XY: 0.190 AC XY: 14146 AN XY: 74390

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.210

Alfa AF: 0.134 Hom.: 327

Bravo AF: 0.193

Asia WGS AF: 0.187 AC: 652 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	1.9
Dann	Benign	0.58

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: rs2072324; hg19: chr17-26116896;