dbSNP rs1443877600: MIB2:c.-251C>T (chr1-1615512-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.-251C>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 0.00000508 in 1,377,712 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: not found (cov: 34)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

MIB2
NM_001170687.4 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.17

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=0.06679368).

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.-251C>T	5_prime_UTR	Exon 1 of 20	NP_001164158.3	Q96AX9-1
MIB2	NM_080875.5		c.-293C>T	5_prime_UTR	Exon 1 of 20	NP_543151.4	E9PD12
MIB2	NM_001170686.4		c.-293C>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.-251C>T	5_prime_UTR	Exon 1 of 20	ENSP00000348081.6	Q96AX9-1
MIB2	ENST00000505820.7	TSL:1	c.-293C>T	5_prime_UTR	Exon 1 of 20	ENSP00000426103.3	Q96AX9-1
MIB2	ENST00000520777.6	TSL:1	c.-293C>T	5_prime_UTR	Exon 1 of 20	ENSP00000428660.2	Q96AX9-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000238

AC:

AN:

126110

AF XY:

0.0000434

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000308

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000508

AC:

AN:

1377712

Hom.:

Cov.:

AF XY:

0.00000588

AC XY:

AN XY:

680012

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30246

American (AMR)

AF:

0.00

AC:

AN:

35366

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24926

East Asian (EAS)

AF:

0.000171

AC:

AN:

35002

South Asian (SAS)

AF:

0.00

AC:

AN:

78232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4888

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076854

Other (OTH)

AF:

0.0000174

AC:

AN:

57584

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

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

0.13

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.3

(source)

DANN

Benign

0.97

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.55

M_CAP

Benign

0.022

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.0

PhyloP100

-1.2

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.19

REVEL

Benign

0.071

Sift

Uncertain

0.015

Sift4G

Pathogenic

0.0

Vest4

0.094

MutPred

0.19

Gain of sheet (P = 0.0149)

MVP

0.12

MPC

0.45

ClinPred

0.093

GERP RS

1.5

PromoterAI

0.028

Neutral

(source)

gMVP

0.068

Mutation Taster

=288/12

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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