rs3729966

Variant names:

• chr17-27774211-G-A
• rs3729966
• NM_000625.4:c.1476+46C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-27774211-G-A
• chr17-27774211-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 rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.1476+46C>T		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.1476+46C>T		intron_variant	Intron 12 of 26	1	NM_000625.4	ENSP00000327251.6

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

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 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;