Genetic Variant MVB12B:p.Pro16del (chr9-126326965-CCCG-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP3BP6

The NM_033446.3(MVB12B):c.47_49delCGC(p.Pro16del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 261,648 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0038 ( 0 hom. )

Consequence

MVB12B
NM_033446.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.40

Publications

0 publications found

Variant links:

Genes affected

MVB12B (HGNC:23368): (multivesicular body subunit 12B) The protein encoded by this gene is a component of the ESCRT-I complex, a heterotetramer, which mediates the sorting of ubiquitinated cargo protein from the plasma membrane to the endosomal vesicle. ESCRT-I complex plays an essential role in HIV budding and endosomal protein sorting. Depletion and overexpression of this and related protein (MVB12A) inhibit HIV-1 infectivity and induce unusual viral assembly defects, indicating a role for MVB12 subunits in regulating ESCRT-mediated virus budding. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

MVB12B links:

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ACMG classification

Classification was made for transcript

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

BP3

Nonframeshift variant in repetitive region in NM_033446.3

BP6

Variant 9-126326965-CCCG-C is Benign according to our data. Variant chr9-126326965-CCCG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3042318.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033446.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVB12B	NM_033446.3	MANE Select	c.47_49delCGC	p.Pro16del	disruptive_inframe_deletion	Exon 1 of 10	NP_258257.1	Q9H7P6-1
	MVB12B	NM_001011703.3		c.47_49delCGC	p.Pro16del	disruptive_inframe_deletion	Exon 1 of 6	NP_001011703.1	Q9H7P6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MVB12B	ENST00000361171.8	TSL:2 MANE Select	c.47_49delCGC	p.Pro16del	disruptive_inframe_deletion	Exon 1 of 10	ENSP00000354772.3	Q9H7P6-1
MVB12B	ENST00000489637.3	TSL:1	c.47_49delCGC	p.Pro16del	disruptive_inframe_deletion	Exon 1 of 6	ENSP00000485994.1	Q9H7P6-2
MVB12B	ENST00000885963.1		c.47_49delCGC	p.Pro16del	disruptive_inframe_deletion	Exon 1 of 11	ENSP00000556022.1

Frequencies

GnomAD3 genomes

AF:

0.0000208

AC:

AN:

143956

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:

0.000366

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00217

AC:

AN:

36018

AF XY:

0.00217

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00250

Gnomad ASJ exome

AF:

0.00140

Gnomad EAS exome

AF:

0.00294

Gnomad FIN exome

AF:

0.00168

Gnomad NFE exome

AF:

0.00256

Gnomad OTH exome

AF:

0.000940

GnomAD4 exome

AF:

0.00376

AC:

442

AN:

117592

Hom.:

AF XY:

0.00365

AC XY:

273

AN XY:

74768

show subpopulations

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

African (AFR)

AF:

0.00221

AC:

AN:

1814

American (AMR)

AF:

0.00228

AC:

AN:

7878

Ashkenazi Jewish (ASJ)

AF:

0.00372

AC:

AN:

4568

East Asian (EAS)

AF:

0.000953

AC:

AN:

2098

South Asian (SAS)

AF:

0.00428

AC:

109

AN:

25456

European-Finnish (FIN)

AF:

0.00545

AC:

AN:

5508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

430

European-Non Finnish (NFE)

AF:

0.00367

AC:

238

AN:

64870

Other (OTH)

AF:

0.00483

AC:

AN:

4970

⚠️ 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: 0.235

Heterozygous variant carriers

165

247

330

412

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:

0.0000208

AC:

AN:

144056

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70118

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

40280

American (AMR)

AF:

0.00

AC:

AN:

14632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3350

East Asian (EAS)

AF:

0.00

AC:

AN:

4934

South Asian (SAS)

AF:

0.00

AC:

AN:

4704

European-Finnish (FIN)

AF:

0.000366

AC:

AN:

8202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64786

Other (OTH)

AF:

0.00

AC:

AN:

2014

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

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

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MVB12B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Mutation Taster

=72/28

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over