Variant chr17-27798892-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000313735.11(NOS2):c.-73-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 886,886 control chromosomes in the GnomAD database, including 53,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.34 ( 8780 hom., cov: 31)

Exomes 𝑓: 0.35 ( 44784 hom. )

Consequence

NOS2
ENST00000313735.11 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001112

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.663

Variant links:

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]

NOS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 17-27798892-G-A is Benign according to our data. Variant chr17-27798892-G-A is described in ClinVar as [Benign]. Clinvar id is 2688120.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS2	NM_000625.4 linkuse as main transcript	c.-73-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11 linkuse as main transcript	c.-73-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000625.4	ENSP00000327251	P2	P35228-1
NOS2	ENST00000697337.1 linkuse as main transcript			upstream_gene_variant				ENSP00000513259

Frequencies

GnomAD3 genomes

AF:

0.336

AC:

51076

AN:

151856

Hom.:

8777

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.407

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.423

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.337

Gnomad OTH

AF:

0.329

GnomAD3 exomes

AF:

0.367

AC:

76702

AN:

209188

Hom.:

14076

AF XY:

0.366

AC XY:

41041

AN XY:

112206

show subpopulations

Gnomad AFR exome

AF:

0.309

Gnomad AMR exome

AF:

0.480

Gnomad ASJ exome

AF:

0.361

Gnomad EAS exome

AF:

0.329

Gnomad SAS exome

AF:

0.415

Gnomad FIN exome

AF:

0.334

Gnomad NFE exome

AF:

0.338

Gnomad OTH exome

AF:

0.358

GnomAD4 exome

AF:

0.348

AC:

255688

AN:

734912

Hom.:

44784

Cov.:

AF XY:

0.350

AC XY:

136515

AN XY:

390148

show subpopulations

Gnomad4 AFR exome

AF:

0.308

Gnomad4 AMR exome

AF:

0.470

Gnomad4 ASJ exome

AF:

0.358

Gnomad4 EAS exome

AF:

0.354

Gnomad4 SAS exome

AF:

0.408

Gnomad4 FIN exome

AF:

0.329

Gnomad4 NFE exome

AF:

0.331

Gnomad4 OTH exome

AF:

0.342

GnomAD4 genome

AF:

0.336

AC:

51116

AN:

151974

Hom.:

8780

Cov.:

AF XY:

0.341

AC XY:

25320

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.305

Gnomad4 AMR

AF:

0.407

Gnomad4 ASJ

AF:

0.353

Gnomad4 EAS

AF:

0.315

Gnomad4 SAS

AF:

0.424

Gnomad4 FIN

AF:

0.324

Gnomad4 NFE

AF:

0.337

Gnomad4 OTH

AF:

0.330

Alfa

AF:

0.336

Hom.:

9152

Bravo

AF:

0.338

Asia WGS

AF:

0.374

AC:

1302

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 48. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over