Genetic Variant MIB2:c.-151C>T (chr1-1615612-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.-151C>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 0.00000191 in 1,569,780 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 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MIB2
NM_001170687.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.758

Publications

6 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:

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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 (BayesDel_noAF=-0.9).

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.-151C>T	5_prime_UTR	Exon 1 of 20	NP_001164158.3	Q96AX9-1
MIB2	NM_080875.5		c.-193C>T	5_prime_UTR	Exon 1 of 20	NP_543151.4	E9PD12
MIB2	NM_001170686.4		c.-193C>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.-151C>T	5_prime_UTR	Exon 1 of 20	ENSP00000348081.6	Q96AX9-1
MIB2	ENST00000505820.7	TSL:1	c.-193C>T	5_prime_UTR	Exon 1 of 20	ENSP00000426103.3	Q96AX9-1
MIB2	ENST00000520777.6	TSL:1	c.-193C>T	5_prime_UTR	Exon 1 of 20	ENSP00000428660.2	Q96AX9-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1417588

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

702828

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

30994

American (AMR)

AF:

0.00

AC:

AN:

40992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25296

East Asian (EAS)

AF:

0.00

AC:

AN:

36322

South Asian (SAS)

AF:

0.00

AC:

AN:

80678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5294

European-Non Finnish (NFE)

AF:

9.14e-7

AC:

AN:

1094192

Other (OTH)

AF:

0.0000170

AC:

AN:

58748

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

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:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.0

(source)

DANN

Benign

0.82

PhyloP100

-0.76

PromoterAI

0.030

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=298/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over