5-14664886-CCGGCGCGGGAGGCGGCGGCCA-C

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]

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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
OTULINNM_138348.6 linkc.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 Appris UniProt
OTULINENST00000284274.5 linkc.72_92delGGCGGCGGCCACGGCGCGGGA p.Glu24_Arg30del disruptive_inframe_deletion Exon 1 of 7 1 NM_138348.6 ENSP00000284274.4 Q96BN8
OTULINENST00000503023.2 linkn.72_92delGGCGGCGGCCACGGCGCGGGA non_coding_transcript_exon_variant Exon 1 of 6 5 ENSP00000427016.1 D6RD57
OTULINENST00000507335.1 linkn.166_186delGGCGGCGGCCACGGCGCGGGA non_coding_transcript_exon_variant Exon 1 of 2 2
OTULINENST00000697367.1 linkn.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.:
34
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:
6
AN:
2102
Hom.:
0
AF XY:
0.00
AC XY:
0
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.:
34
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.:
10
Asia WGS
AF:
0.0130
AC:
44
AN:
3430

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 03, 2025- -

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.

Other links and lift over

dbSNP: rs199656228; hg19: chr5-14664995; API