rs3729508

chr17-27782004-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.722+11A>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 1,611,480 control chromosomes in the GnomAD database, including 307,006 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.67 (34483 hom., cov: 32)
  • Exomes 𝑓: 0.61 (272523 hom.)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.16

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=-0.83).
• BP6: Variant 17-27782004-T-C is Benign according to our data. Variant chr17-27782004-T-C is described in ClinVar as [Benign]. Clinvar id is 2687961.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS2	NM_000625.4	c.722+11A>G		intron_variant		ENST00000313735.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS2	ENST00000313735.11	c.722+11A>G		intron_variant		1	NM_000625.4	P2

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101331 AN: 151932 Hom.: 34425 Cov.: 32

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.659

GnomAD3 exomes AF: 0.640 AC: 160086 AN: 250122 Hom.: 52025 AF XY: 0.640 AC XY: 86463 AN XY: 135134

Gnomad AFR exome AF: 0.804

Gnomad AMR exome AF: 0.713

Gnomad ASJ exome AF: 0.648

Gnomad EAS exome AF: 0.525

Gnomad SAS exome AF: 0.733

Gnomad FIN exome AF: 0.600

Gnomad NFE exome AF: 0.595

Gnomad OTH exome AF: 0.639

GnomAD4 exome AF: 0.608 AC: 887227 AN: 1459430 Hom.: 272523 Cov.: 33 AF XY: 0.611 AC XY: 443554 AN XY: 726084

Gnomad4 AFR exome AF: 0.812

Gnomad4 AMR exome AF: 0.709

Gnomad4 ASJ exome AF: 0.652

Gnomad4 EAS exome AF: 0.506

Gnomad4 SAS exome AF: 0.730

Gnomad4 FIN exome AF: 0.599

Gnomad4 NFE exome AF: 0.590

Gnomad4 OTH exome AF: 0.624

GnomAD4 genome AF: 0.667 AC: 101451 AN: 152050 Hom.: 34483 Cov.: 32 AF XY: 0.670 AC XY: 49813 AN XY: 74328

Gnomad4 AFR AF: 0.800

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.660

Alfa AF: 0.612 Hom.: 41398

Bravo AF: 0.677

Asia WGS AF: 0.629 AC: 2191 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	-0.83
Cadd	Benign	0.93
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3729508; hg19: chr17-26109030;