Variant 18-21741286-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_020774.4(MIB1):c.-298G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 158,852 control chromosomes in the GnomAD database, including 3,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3218 hom., cov: 33)

Exomes 𝑓: 0.19 ( 148 hom. )

Consequence

MIB1
NM_020774.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.46

Variant links:

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 links:

MIB1 (HGNC:):

MIB1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 18-21741286-G-A is Benign according to our data. Variant chr18-21741286-G-A is described in ClinVar as [Benign]. Clinvar id is 668990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIB1	NM_020774.4 linkuse as main transcript	c.-298G>A		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 linkuse as main transcript	c.-298G>A		5_prime_UTR_variant	1/21	1	NM_020774.4	ENSP00000261537.6		Q86YT6
MIB1	ENST00000578646.5 linkuse as main transcript	n.168-24486G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28205

AN:

151558

Hom.:

3219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0925

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.194

Gnomad OTH

AF:

0.183

GnomAD4 exome

AF:

0.192

AC:

1381

AN:

7186

Hom.:

148

Cov.:

AF XY:

0.191

AC XY:

735

AN XY:

3844

show subpopulations

Gnomad4 AFR exome

AF:

0.0662

Gnomad4 AMR exome

AF:

0.222

Gnomad4 ASJ exome

AF:

0.222

Gnomad4 EAS exome

AF:

0.356

Gnomad4 SAS exome

AF:

0.328

Gnomad4 FIN exome

AF:

0.205

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.203

GnomAD4 genome

AF:

0.186

AC:

28208

AN:

151666

Hom.:

3218

Cov.:

AF XY:

0.194

AC XY:

14399

AN XY:

74132

show subpopulations

Gnomad4 AFR

AF:

0.0924

Gnomad4 AMR

AF:

0.241

Gnomad4 ASJ

AF:

0.179

Gnomad4 EAS

AF:

0.382

Gnomad4 SAS

AF:

0.399

Gnomad4 FIN

AF:

0.227

Gnomad4 NFE

AF:

0.194

Gnomad4 OTH

AF:

0.187

Alfa

AF:

0.183

Hom.:

454

Bravo

AF:

0.177

Asia WGS

AF:

0.392

AC:

1340

AN:

3426

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 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

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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