Variant 5-14664886-CCGGCGCGGGAGGCGGCGGCCA-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBA1

The NM_138348.6(OTULIN):c.72_92delGGCGGCGGCCACGGCGCGGGA(p.Glu24_Arg30del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0075 in 1,190,212 control chromosomes in the GnomAD database, including 330 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.029 ( 170 hom., cov: 34)

Exomes 𝑓: 0.0044 ( 160 hom. )

Consequence

OTULIN
NM_138348.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.13

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 -8 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_138348.6.

BP6

Variant 5-14664886-CCGGCGCGGGAGGCGGCGGCCA-C is Benign according to our data. Variant chr5-14664886-CCGGCGCGGGAGGCGGCGGCCA-C is described in ClinVar as [Benign]. Clinvar id is 1165553.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTULIN	NM_138348.6 link	c.72_92delGGCGGCGGCCACGGCGCGGGA	p.Glu24_Arg30del	disruptive_inframe_deletion	Exon 1 of 7	ENST00000284274.5	NP_612357.4	Q96BN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OTULIN	ENST00000284274.5 link	c.72_92delGGCGGCGGCCACGGCGCGGGA	p.Glu24_Arg30del	disruptive_inframe_deletion	Exon 1 of 7	1	NM_138348.6	ENSP00000284274.4	Q96BN8
OTULIN	ENST00000503023.2 link	n.72_92delGGCGGCGGCCACGGCGCGGGA		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000427016.1	D6RD57
OTULIN	ENST00000507335.1 link	n.166_186delGGCGGCGGCCACGGCGCGGGA		non_coding_transcript_exon_variant	Exon 1 of 2	2
OTULIN	ENST00000697367.1 link	n.72_92delGGCGGCGGCCACGGCGCGGGA		non_coding_transcript_exon_variant	Exon 1 of 5			ENSP00000513279.1	A0A8V8TKZ0

Frequencies

GnomAD3 genomes

AF:

0.0286

AC:

4314

AN:

151006

Hom.:

169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0934

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.0169

Gnomad FIN

AF:

0.0000991

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00216

Gnomad OTH

AF:

0.0227

GnomAD3 exomes

AF:

0.00285

AC:

AN:

2102

Hom.:

AF XY:

0.00

AC XY:

AN XY:

1230

show subpopulations

Gnomad AFR exome

AF:

0.0455

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0714

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00443

AC:

4601

AN:

1039098

Hom.:

160

AF XY:

0.00425

AC XY:

2084

AN XY:

490630

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.00771

Gnomad4 ASJ exome

AF:

0.00261

Gnomad4 EAS exome

AF:

0.00124

Gnomad4 SAS exome

AF:

0.0157

Gnomad4 FIN exome

AF:

0.000413

Gnomad4 NFE exome

AF:

0.00151

Gnomad4 OTH exome

AF:

0.00976

GnomAD4 genome

AF:

0.0286

AC:

4325

AN:

151114

Hom.:

170

Cov.:

AF XY:

0.0272

AC XY:

2011

AN XY:

73850

show subpopulations

Gnomad4 AFR

AF:

0.0934

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000774

Gnomad4 SAS

AF:

0.0174

Gnomad4 FIN

AF:

0.0000991

Gnomad4 NFE

AF:

0.00214

Gnomad4 OTH

AF:

0.0224

Alfa

AF:

0.0168

Hom.:

Asia WGS

AF:

0.0130

AC:

AN:

3430

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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