17-27773295-A-G

Variant names:

• chr17-27773295-A-G
• rs2248814
• NM_000625.4:c.1477-52T>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.1477-52T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 1,358,722 control chromosomes in the GnomAD database, including 279,574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (35728 hom., cov: 31)
  • Exomes 𝑓: 0.63 (243846 hom.)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.62

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=-0.92).
• BP6: Variant 17-27773295-A-G is Benign according to our data. Variant chr17-27773295-A-G is described in ClinVar as [Benign]. Clinvar id is 2687962.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.1477-52T>C		intron_variant	Intron 12 of 26	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.1477-52T>C		intron_variant	Intron 12 of 26	1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103137 AN: 151914 Hom.: 35672 Cov.: 31

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.688

GnomAD3 exomes AF: 0.651 AC: 156524 AN: 240592 Hom.: 51918 AF XY: 0.656 AC XY: 85791 AN XY: 130766

Gnomad AFR exome AF: 0.814

Gnomad AMR exome AF: 0.618

Gnomad ASJ exome AF: 0.695

Gnomad EAS exome AF: 0.679

Gnomad SAS exome AF: 0.799

Gnomad FIN exome AF: 0.557

Gnomad NFE exome AF: 0.606

Gnomad OTH exome AF: 0.651

GnomAD4 exome AF: 0.632 AC: 762962 AN: 1206692 Hom.: 243846 Cov.: 16 AF XY: 0.638 AC XY: 391115 AN XY: 613298

Gnomad4 AFR exome AF: 0.824

Gnomad4 AMR exome AF: 0.621

Gnomad4 ASJ exome AF: 0.700

Gnomad4 EAS exome AF: 0.727

Gnomad4 SAS exome AF: 0.796

Gnomad4 FIN exome AF: 0.558

Gnomad4 NFE exome AF: 0.608

Gnomad4 OTH exome AF: 0.653

GnomAD4 genome AF: 0.679 AC: 103253 AN: 152030 Hom.: 35728 Cov.: 31 AF XY: 0.680 AC XY: 50501 AN XY: 74300

Gnomad4 AFR AF: 0.809

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.801

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.690

Alfa AF: 0.592 Hom.: 3500

Bravo AF: 0.686

Asia WGS AF: 0.762 AC: 2651 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 85% of patients studied by a panel of primary immunodeficiencies. Number of patients: 81. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.28

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: rs2248814; hg19: chr17-26100321;