rs3729966

chr17-27774211-G-Achr17-27774211-G-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.1476+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,366,358 control chromosomes in the GnomAD database, including 33,411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3124 hom., cov: 32)
  • Exomes 𝑓: 0.22 (30287 hom.)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.961

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 17-27774211-G-A is Benign according to our data. Variant chr17-27774211-G-A is described in ClinVar as [Benign]. Clinvar id is 2688145.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS2	NM_000625.4	c.1476+46C>T		intron_variant		ENST00000313735.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS2	ENST00000313735.11	c.1476+46C>T		intron_variant		1	NM_000625.4	P2

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29929 AN: 151696 Hom.: 3125 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.213

GnomAD3 exomes AF: 0.214 AC: 26684 AN: 124684 Hom.: 2957 AF XY: 0.214 AC XY: 14186 AN XY: 66340

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.297

Gnomad ASJ exome AF: 0.173

Gnomad EAS exome AF: 0.293

Gnomad SAS exome AF: 0.260

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.203

GnomAD4 exome AF: 0.221 AC: 268520 AN: 1214544 Hom.: 30287 Cov.: 18 AF XY: 0.222 AC XY: 131494 AN XY: 593072

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.354

Gnomad4 SAS exome AF: 0.264

Gnomad4 FIN exome AF: 0.184

Gnomad4 NFE exome AF: 0.218

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.197 AC: 29938 AN: 151814 Hom.: 3124 Cov.: 32 AF XY: 0.198 AC XY: 14684 AN XY: 74182

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.211

Alfa AF: 0.193 Hom.: 561

Bravo AF: 0.198

Asia WGS AF: 0.255 AC: 890 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 45% of patients studied by a panel of primary immunodeficiencies. Number of patients: 43. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.24
Dann	Benign	0.67

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: rs3729966; hg19: chr17-26101237; COSMIC: COSV58225806;