dbSNP rs2286886: MVB12B:c.814-75T>C (chr9-126483898-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033446.3(MVB12B):c.814-75T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 1,479,746 control chromosomes in the GnomAD database, including 152,546 homozygotes. 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 0.40 ( 13165 hom., cov: 33)

Exomes 𝑓: 0.45 ( 139381 hom. )

Consequence

MVB12B
NM_033446.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.866

Publications

10 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MVB12B	NM_033446.3 link	c.814-75T>C		intron_variant	Intron 8 of 9	ENST00000361171.8	NP_258257.1	Q9H7P6-1A0A024R8B8
MVB12B	XM_005252297.1 link	c.769-75T>C		intron_variant	Intron 8 of 9		XP_005252354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MVB12B	ENST00000361171.8 link	c.814-75T>C		intron_variant	Intron 8 of 9	2	NM_033446.3	ENSP00000354772.3		Q9H7P6-1
MVB12B	ENST00000485886.1 link	n.613-75T>C		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61344

AN:

151960

Hom.:

13156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.265

Gnomad AMI

AF:

0.403

Gnomad AMR

AF:

0.432

Gnomad ASJ

AF:

0.495

Gnomad EAS

AF:

0.708

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.445

Gnomad OTH

AF:

0.441

GnomAD4 exome

AF:

0.453

AC:

601507

AN:

1327666

Hom.:

139381

AF XY:

0.450

AC XY:

299688

AN XY:

666476

show subpopulations

African (AFR)

AF:

0.259

AC:

8007

AN:

30966

American (AMR)

AF:

0.484

AC:

21220

AN:

43848

Ashkenazi Jewish (ASJ)

AF:

0.490

AC:

12077

AN:

24622

East Asian (EAS)

AF:

0.706

AC:

27552

AN:

39000

South Asian (SAS)

AF:

0.376

AC:

30790

AN:

81896

European-Finnish (FIN)

AF:

0.443

AC:

23352

AN:

52764

Middle Eastern (MID)

AF:

0.400

AC:

2193

AN:

5484

European-Non Finnish (NFE)

AF:

0.453

AC:

450098

AN:

993236

Other (OTH)

AF:

0.469

AC:

26218

AN:

55850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

16123

32246

48369

64492

80615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13084

26168

39252

52336

65420

<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:

0.404

AC:

61373

AN:

152080

Hom.:

13165

Cov.:

AF XY:

0.404

AC XY:

30046

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.265

AC:

11006

AN:

41482

American (AMR)

AF:

0.432

AC:

6607

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.495

AC:

1716

AN:

3468

East Asian (EAS)

AF:

0.708

AC:

3648

AN:

5152

South Asian (SAS)

AF:

0.395

AC:

1907

AN:

4822

European-Finnish (FIN)

AF:

0.456

AC:

4820

AN:

10578

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.445

AC:

30255

AN:

67978

Other (OTH)

AF:

0.438

AC:

924

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1859

3719

5578

7438

9297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

576

1152

1728

2304

2880

<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:

0.438

Hom.:

56686

Bravo

AF:

0.406

Asia WGS

AF:

0.546

AC:

1898

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.29

(source)

DANN

Benign

0.48

PhyloP100

-0.87

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over