chr5-14664712-G-C

Variant names:

• chr5-14664712-G-C
• rs250435
• ENST00000921417.1:c.-114G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000921417.1(OTULIN):​c.-114G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000675 in 1,036,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 35)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: OTULIN ENST00000921417.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 7 publications found

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-DT (HGNC:55368): (OTULIN divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000921417.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTULIN	NM_138348.6	MANE Select	c.-114G>C		upstream_gene	N/A	NP_612357.4
	OTULIN-DT	NR_168439.1		n.-108C>G		upstream_gene	N/A
	OTULIN-DT	NR_168440.1		n.-108C>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTULIN	ENST00000921417.1		c.-114G>C		5_prime_UTR	Exon 1 of 7	ENSP00000591476.1
	OTULIN	ENST00000955678.1		c.-114G>C		5_prime_UTR	Exon 1 of 6	ENSP00000625737.1
	OTULIN	ENST00000503023.2	TSL:5	n.-114G>C		non_coding_transcript_exon	Exon 1 of 6	ENSP00000427016.1	D6RD57

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152102 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000452 AC: 4 AN: 884718 Hom.: 0 Cov.: 13 AF XY: 0.00000480 AC XY: 2 AN XY: 416626

African (AFR) AF: 0.00 AC: 0 AN: 17112

American (AMR) AF: 0.00 AC: 0 AN: 3866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8074

East Asian (EAS) AF: 0.00 AC: 0 AN: 13086

South Asian (SAS) AF: 0.00 AC: 0 AN: 16464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2044

European-Non Finnish (NFE) AF: 0.00000512 AC: 4 AN: 780670

Other (OTH) AF: 0.00 AC: 0 AN: 31696

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152102 Hom.: 0 Cov.: 35 AF XY: 0.0000269 AC XY: 2 AN XY: 74290

African (AFR) AF: 0.0000483 AC: 2 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 3032

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.75
DANN	Benign	0.41
PhyloP100		-0.24
PromoterAI		-0.11	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs250435; hg19: chr5-14664821;