Variant 9-126395571-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_033446.3(MVB12B):c.540-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,613,420 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 2 hom. )

Consequence

MVB12B
NM_033446.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002417

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.619

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 made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 9-126395571-A-G is Benign according to our data. Variant chr9-126395571-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3052638.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MVB12B	NM_033446.3 linkuse as main transcript	c.540-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000361171.8	NP_258257.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
MVB12B	ENST00000361171.8 linkuse as main transcript	c.540-4A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2	NM_033446.3	ENSP00000354772	P1	Q9H7P6-1
MVB12B	ENST00000489637.3 linkuse as main transcript	c.540-4A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000485994		Q9H7P6-2
MVB12B	ENST00000402437.2 linkuse as main transcript	c.495-4A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	3		ENSP00000384751

Frequencies

GnomAD3 genomes

AF:

0.00143

AC:

217

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00235

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00237

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00139

AC:

348

AN:

250632

Hom.:

AF XY:

0.00144

AC XY:

195

AN XY:

135478

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00231

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.00213

AC:

3108

AN:

1461148

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

1509

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00234

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00261

Gnomad4 OTH exome

AF:

0.00134

GnomAD4 genome

AF:

0.00143

AC:

218

AN:

152272

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00238

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00186

Hom.:

Bravo

AF:

0.00165

EpiCase

AF:

0.00333

EpiControl

AF:

0.00362

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MVB12B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

9.0

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00024

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over