Variant chr9-126381156-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_033446.3(MVB12B):c.297A>G(p.Ser99=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,612,318 control chromosomes in the GnomAD database, including 11,160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.094 ( 913 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10247 hom. )

Consequence

MVB12B
NM_033446.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.471

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 9-126381156-A-G is Benign according to our data. Variant chr9-126381156-A-G is described in ClinVar as [Benign]. Clinvar id is 3061019.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.471 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MVB12B	NM_033446.3 linkuse as main transcript	c.297A>G	p.Ser99=	synonymous_variant	3/10	ENST00000361171.8	NP_258257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MVB12B	ENST00000361171.8 linkuse as main transcript	c.297A>G	p.Ser99=	synonymous_variant	3/10	2	NM_033446.3	ENSP00000354772	P1	Q9H7P6-1
MVB12B	ENST00000489637.3 linkuse as main transcript	c.297A>G	p.Ser99=	synonymous_variant	3/6	1		ENSP00000485994		Q9H7P6-2
MVB12B	ENST00000402437.2 linkuse as main transcript	c.252A>G	p.Ser84=	synonymous_variant	3/6	3		ENSP00000384751

Frequencies

GnomAD3 genomes

AF:

0.0947

AC:

14400

AN:

152134

Hom.:

915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0229

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.132

AC:

33130

AN:

251212

Hom.:

2744

AF XY:

0.132

AC XY:

17881

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.0177

Gnomad AMR exome

AF:

0.180

Gnomad ASJ exome

AF:

0.171

Gnomad EAS exome

AF:

0.269

Gnomad SAS exome

AF:

0.152

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.106

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.111

AC:

162188

AN:

1460066

Hom.:

10247

Cov.:

AF XY:

0.113

AC XY:

82012

AN XY:

726498

show subpopulations

Gnomad4 AFR exome

AF:

0.0168

Gnomad4 AMR exome

AF:

0.174

Gnomad4 ASJ exome

AF:

0.171

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.101

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.0945

AC:

14387

AN:

152252

Hom.:

913

Cov.:

AF XY:

0.0974

AC XY:

7253

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0229

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.255

Gnomad4 SAS

AF:

0.168

Gnomad4 FIN

AF:

0.118

Gnomad4 NFE

AF:

0.107

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.108

Hom.:

1613

Bravo

AF:

0.0936

Asia WGS

AF:

0.204

AC:

708

AN:

3478

EpiCase

AF:

0.105

EpiControl

AF:

0.108

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MVB12B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as 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

-0.44

CADD

Benign

7.2

DANN

Benign

0.68

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

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