Variant chr5-14664712-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 ENST00000503023.2(OTULIN):c.-114G>A variant causes a 5 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 1,036,328 control chromosomes in the GnomAD database, including 446,427 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.93 ( 65348 hom., cov: 35)

Exomes 𝑓: 0.93 ( 381079 hom. )

Consequence

OTULIN
ENST00000503023.2 5_prime_UTR, NMD_transcript

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.244

Variant links:

Genes affected

OTULIN (HGNC:25118): (OTU deubiquitinase with linear linkage specificity) This gene encodes a member of the peptidase C65 family of ubiquitin isopeptidases. Members of this family remove ubiquitin from proteins. The encoded enzyme specifically recognizes and removes M1(Met1)-linked, or linear, ubiquitin chains from protein substrates. Linear ubiquitin chains are known to regulate the NF-kappa B signaling pathway in the context of immunity and inflammation. Mutations in this gene cause a potentially fatal autoinflammatory syndrome in human patients. [provided by RefSeq, Sep 2016]

OTULIN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 5-14664712-G-A is Benign according to our data. Variant chr5-14664712-G-A is described in ClinVar as [Benign]. Clinvar id is 2688224.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTULIN	NM_138348.6 linkuse as main transcript			upstream_gene_variant		ENST00000284274.5	NP_612357.4

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
OTULIN	ENST00000503023.2 linkuse as main transcript	c.-114G>A	5_prime_UTR_variant, NMD_transcript_variant	1/6	5		ENSP00000427016
OTULIN	ENST00000284274.5 linkuse as main transcript		upstream_gene_variant		1	NM_138348.6	ENSP00000284274	P1
OTULIN	ENST00000507335.1 linkuse as main transcript		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.926

AC:

140906

AN:

152094

Hom.:

65321

Cov.:

show subpopulations

Gnomad AFR

AF:

0.918

Gnomad AMI

AF:

0.975

Gnomad AMR

AF:

0.957

Gnomad ASJ

AF:

0.929

Gnomad EAS

AF:

0.817

Gnomad SAS

AF:

0.912

Gnomad FIN

AF:

0.944

Gnomad MID

AF:

0.978

Gnomad NFE

AF:

0.930

Gnomad OTH

AF:

0.930

GnomAD4 exome

AF:

0.928

AC:

820685

AN:

884126

Hom.:

381079

Cov.:

AF XY:

0.928

AC XY:

386481

AN XY:

416326

show subpopulations

Gnomad4 AFR exome

AF:

0.919

Gnomad4 AMR exome

AF:

0.966

Gnomad4 ASJ exome

AF:

0.937

Gnomad4 EAS exome

AF:

0.800

Gnomad4 SAS exome

AF:

0.918

Gnomad4 FIN exome

AF:

0.941

Gnomad4 NFE exome

AF:

0.930

Gnomad4 OTH exome

AF:

0.926

GnomAD4 genome

AF:

0.926

AC:

140978

AN:

152202

Hom.:

65348

Cov.:

AF XY:

0.926

AC XY:

68867

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.918

Gnomad4 AMR

AF:

0.957

Gnomad4 ASJ

AF:

0.929

Gnomad4 EAS

AF:

0.817

Gnomad4 SAS

AF:

0.912

Gnomad4 FIN

AF:

0.944

Gnomad4 NFE

AF:

0.930

Gnomad4 OTH

AF:

0.921

Alfa

AF:

0.920

Hom.:

3032

Bravo

AF:

0.929

Asia WGS

AF:

0.846

AC:

2931

AN:

3466

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 33% of patients studied by a panel of primary immunodeficiencies. Number of patients: 31. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.8

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

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