rs2297520

chr17-27781014-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000625.4(NOS2):c.864+22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 1,608,076 control chromosomes in the GnomAD database, including 306,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.67 (34653 hom., cov: 34)
  • Exomes 𝑓: 0.61 (271707 hom.)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.531

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-27781014-T-C is Benign according to our data. Variant chr17-27781014-T-C is described in ClinVar as [Benign]. Clinvar id is 2687960.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS2	NM_000625.4	c.864+22A>G		intron_variant		ENST00000313735.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS2	ENST00000313735.11	c.864+22A>G		intron_variant		1	NM_000625.4	P2

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101629 AN: 152060 Hom.: 34595 Cov.: 34

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.656

GnomAD3 exomes AF: 0.641 AC: 158540 AN: 247328 Hom.: 51682 AF XY: 0.641 AC XY: 85755 AN XY: 133834

Gnomad AFR exome AF: 0.807

Gnomad AMR exome AF: 0.713

Gnomad ASJ exome AF: 0.648

Gnomad EAS exome AF: 0.541

Gnomad SAS exome AF: 0.733

Gnomad FIN exome AF: 0.600

Gnomad NFE exome AF: 0.594

Gnomad OTH exome AF: 0.637

GnomAD4 exome AF: 0.608 AC: 884905 AN: 1455898 Hom.: 271707 Cov.: 57 AF XY: 0.611 AC XY: 441875 AN XY: 723412

Gnomad4 AFR exome AF: 0.817

Gnomad4 AMR exome AF: 0.710

Gnomad4 ASJ exome AF: 0.651

Gnomad4 EAS exome AF: 0.523

Gnomad4 SAS exome AF: 0.730

Gnomad4 FIN exome AF: 0.599

Gnomad4 NFE exome AF: 0.589

Gnomad4 OTH exome AF: 0.623

GnomAD4 genome AF: 0.669 AC: 101747 AN: 152178 Hom.: 34653 Cov.: 34 AF XY: 0.671 AC XY: 49945 AN XY: 74380

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.658

Alfa AF: 0.633 Hom.: 5673

Bravo AF: 0.679

Asia WGS AF: 0.628 AC: 2188 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 86% of patients studied by a panel of primary immunodeficiencies. Number of patients: 82. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.95
Dann	Benign	0.15

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: rs2297520; hg19: chr17-26108040; COSMIC: COSV58226238;