rs16966545

chr17-27777596-T-A

Variant summary

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

The NM_000625.4(NOS2):c.1281+1094A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,150 control chromosomes in the GnomAD database, including 2,915 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 (2915 hom., cov: 32)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS2	NM_000625.4	c.1281+1094A>T		intron_variant		ENST00000313735.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS2	ENST00000313735.11	c.1281+1094A>T		intron_variant		1	NM_000625.4	P2

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29363 AN: 152030 Hom.: 2915 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.193 AC: 29373 AN: 152150 Hom.: 2915 Cov.: 32 AF XY: 0.193 AC XY: 14342 AN XY: 74390

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.210

Alfa AF: 0.190 Hom.: 355

Bravo AF: 0.194

Asia WGS AF: 0.151 AC: 525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.1
Dann	Benign	0.41

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: rs16966545; hg19: chr17-26104622;