Genetic Variant MIB2:c.-260C>T (chr1-1615503-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001170687.4(MIB2):c.-260C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,528,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

MIB2
NM_001170687.4 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.59

Publications

0 publications found

Variant links:

Genes affected

MIB2 (HGNC:30577): (MIB E3 ubiquitin protein ligase 2) The protein encoded by this gene is an E3 ubiquitin protein ligase that mediates ubiquitination of proteins in the Notch signaling pathway. The encoded protein may be a suppressor of melanoma invasion. [provided by RefSeq, Mar 2017]

MIB2 links:

ENSG00000272106 (HGNC:):

ENSG00000272106 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03768912).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170687.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MIB2	NM_001170687.4	MANE Select	c.-260C>T	5_prime_UTR	Exon 1 of 20	NP_001164158.3	Q96AX9-1
MIB2	NM_080875.5		c.-302C>T	5_prime_UTR	Exon 1 of 20	NP_543151.4	E9PD12
MIB2	NM_001170686.4		c.-302C>T	5_prime_UTR	Exon 1 of 20	NP_001164157.3	Q96AX9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MIB2	ENST00000355826.10	TSL:1 MANE Select	c.-260C>T	5_prime_UTR	Exon 1 of 20	ENSP00000348081.6	Q96AX9-1
MIB2	ENST00000505820.7	TSL:1	c.-302C>T	5_prime_UTR	Exon 1 of 20	ENSP00000426103.3	Q96AX9-1
MIB2	ENST00000520777.6	TSL:1	c.-302C>T	5_prime_UTR	Exon 1 of 20	ENSP00000428660.2	Q96AX9-3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000243

AC:

AN:

123494

AF XY:

0.0000294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000423

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000102

AC:

AN:

1376126

Hom.:

Cov.:

AF XY:

0.00000883

AC XY:

AN XY:

679240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30026

American (AMR)

AF:

0.0000283

AC:

AN:

35300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24890

East Asian (EAS)

AF:

0.0000861

AC:

AN:

34832

South Asian (SAS)

AF:

0.0000384

AC:

AN:

78088

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4704

European-Non Finnish (NFE)

AF:

0.00000464

AC:

AN:

1076444

Other (OTH)

AF:

0.0000348

AC:

AN:

57520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41582

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.000385

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.1

(source)

DANN

Benign

0.74

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.47

M_CAP

Benign

0.016

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.0

PhyloP100

-4.6

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.11

REVEL

Benign

0.015

Sift

Benign

1.0

Sift4G

Benign

0.097

Vest4

0.040

MutPred

0.12

Loss of glycosylation at P15 (P = 0.0522)

MVP

0.040

MPC

0.45

ClinPred

0.035

GERP RS

-2.9

PromoterAI

-0.053

Neutral

(source)

gMVP

0.075

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over