rs3729508

Variant names:

• chr17-27782004-T-C
• rs3729508
• NM_000625.4:c.722+11A>G

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 rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.722+11A>G		intron_variant	Intron 7 of 26	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.722+11A>G		intron_variant	Intron 7 of 26	1	NM_000625.4	ENSP00000327251.6

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

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 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;