18-21741535-AGCGGCGGCGGCGGCG-A

Position:

• chr18-21741535-AGCGGCGGCGGCGGCG-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_020774.4(MIB1):​c.-43_-29delGGCGGCGGCGGCGGC variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00000406 in 1,231,356 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: MIB1 NM_020774.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.00

Genes affected

MIB1 (HGNC:21086): (MIB E3 ubiquitin protein ligase 1) This gene encodes a protein containing multiple ankyrin repeats and RING finger domains that functions as an E3 ubiquitin ligase. The encoded protein positively regulates Notch signaling by ubiquitinating the Notch receptors, thereby facilitating their endocytosis. This protein may also promote the ubiquitination and degradation of death-associated protein kinase 1 (DAPK1). [provided by RefSeq, Jun 2013]

MIB1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 18-21741535-AGCGGCGGCGGCGGCG-A is Benign according to our data. Variant chr18-21741535-AGCGGCGGCGGCGGCG-A is described in ClinVar as [Likely_benign]. Clinvar id is 422751.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIB1	NM_020774.4	c.-43_-29delGGCGGCGGCGGCGGC		5_prime_UTR_variant	1/21	ENST00000261537.7	NP_065825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIB1	ENST00000261537	c.-43_-29delGGCGGCGGCGGCGGC		5_prime_UTR_variant	1/21	1	NM_020774.4	ENSP00000261537.6
MIB1	ENST00000578646.5	n.168-24231_168-24217delGGCGGCGGCGGCGGC		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00000667 AC: 1 AN: 149910 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000977

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000370 AC: 4 AN: 1081446 Hom.: 0 AF XY: 0.00000574 AC XY: 3 AN XY: 523036

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000440

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000667 AC: 1 AN: 149910 Hom.: 0 Cov.: 32 AF XY: 0.0000137 AC XY: 1 AN XY: 73144

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000977

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 22, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs755675508; hg19: chr18-19321496;