dbSNP rs10987251: MVB12B:c.204+85G>A (chr9-126340715-G-A) – 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.204+85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,481,558 control chromosomes in the GnomAD database, including 72,478 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.30 ( 6912 hom., cov: 32)

Exomes 𝑓: 0.31 ( 65566 hom. )

Consequence

MVB12B
NM_033446.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.270

Publications

6 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

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.204+85G>A		intron	N/A	NP_258257.1	Q9H7P6-1
	MVB12B	NM_001011703.3		c.204+85G>A		intron	N/A	NP_001011703.1	Q9H7P6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MVB12B	ENST00000361171.8	TSL:2 MANE Select	c.204+85G>A	intron	N/A	ENSP00000354772.3	Q9H7P6-1
MVB12B	ENST00000489637.3	TSL:1	c.204+85G>A	intron	N/A	ENSP00000485994.1	Q9H7P6-2
MVB12B	ENST00000885963.1		c.204+85G>A	intron	N/A	ENSP00000556022.1

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45572

AN:

151968

Hom.:

6912

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.281

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.255

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.283

GnomAD4 exome

AF:

0.313

AC:

416333

AN:

1329472

Hom.:

65566

AF XY:

0.312

AC XY:

205251

AN XY:

658878

show subpopulations

African (AFR)

AF:

0.274

AC:

8300

AN:

30342

American (AMR)

AF:

0.323

AC:

12720

AN:

39406

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

5794

AN:

22664

East Asian (EAS)

AF:

0.273

AC:

10292

AN:

37740

South Asian (SAS)

AF:

0.280

AC:

21666

AN:

77410

European-Finnish (FIN)

AF:

0.393

AC:

19751

AN:

50206

Middle Eastern (MID)

AF:

0.241

AC:

1099

AN:

4566

European-Non Finnish (NFE)

AF:

0.316

AC:

320385

AN:

1012436

Other (OTH)

AF:

0.298

AC:

16326

AN:

54702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

12614

25229

37843

50458

63072

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10708

21416

32124

42832

53540

<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:

0.300

AC:

45588

AN:

152086

Hom.:

6912

Cov.:

AF XY:

0.302

AC XY:

22485

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.271

AC:

11233

AN:

41506

American (AMR)

AF:

0.274

AC:

4183

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

881

AN:

3462

East Asian (EAS)

AF:

0.280

AC:

1447

AN:

5174

South Asian (SAS)

AF:

0.298

AC:

1438

AN:

4824

European-Finnish (FIN)

AF:

0.394

AC:

4159

AN:

10564

Middle Eastern (MID)

AF:

0.250

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.316

AC:

21457

AN:

67964

Other (OTH)

AF:

0.280

AC:

590

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1640

3281

4921

6562

8202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.313

Hom.:

3979

Bravo

AF:

0.292

Asia WGS

AF:

0.295

AC:

1025

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.0

(source)

DANN

Benign

0.72

PhyloP100

-0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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