dbSNP rs199741261: MIB2:c.-151C>A (chr1-1615612-C-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001170687.4(MIB2):c.-151C>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 0.00118 in 1,569,886 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0012 ( 12 hom. )

Consequence

MIB2
NM_001170687.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.352183).

BP6

Variant 1-1615612-C-A is Benign according to our data. Variant chr1-1615612-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 218832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

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

Frequencies

GnomAD3 genomes

AF:

0.00140

AC:

213

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00222

AC:

405

AN:

182084

AF XY:

0.00234

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00138

Gnomad ASJ exome

AF:

0.0296

Gnomad EAS exome

AF:

0.0000752

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000836

Gnomad OTH exome

AF:

0.00498

GnomAD4 exome

AF:

0.00116

AC:

1643

AN:

1417584

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

824

AN XY:

702824

show subpopulations

African (AFR)

AF:

0.000226

AC:

AN:

30994

American (AMR)

AF:

0.00129

AC:

AN:

40990

Ashkenazi Jewish (ASJ)

AF:

0.0298

AC:

755

AN:

25296

East Asian (EAS)

AF:

0.00

AC:

AN:

36322

South Asian (SAS)

AF:

0.000521

AC:

AN:

80678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45072

Middle Eastern (MID)

AF:

0.00831

AC:

AN:

5294

European-Non Finnish (NFE)

AF:

0.000491

AC:

537

AN:

1094190

Other (OTH)

AF:

0.00349

AC:

205

AN:

58748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

175

263

350

438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00139

AC:

211

AN:

152302

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41574

American (AMR)

AF:

0.000980

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0343

AC:

119

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000897

AC:

AN:

68016

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00218

Hom.:

Bravo

AF:

0.00138

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00169

AC:

ExAC

AF:

0.00113

AC:

134

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.31

CADD

Benign

2.1

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.017

PhyloP100

-0.76

Vest4

0.10

GERP RS

0.43

PromoterAI

0.042

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=179/21

disease causing (fs/PTC)

(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