Variant 8-81758536-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152284.4(CHMP4C):c.694G>A(p.Ala232Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0633 in 1,608,078 control chromosomes in the GnomAD database, including 3,551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.051 ( 224 hom., cov: 32)

Exomes 𝑓: 0.065 ( 3327 hom. )

Consequence

CHMP4C
NM_152284.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.15

Variant links:

Genes affected

CHMP4C (HGNC:30599): (charged multivesicular body protein 4C) CHMP4C belongs to the chromatin-modifying protein/charged multivesicular body protein (CHMP) family. These proteins are components of ESCRT-III (endosomal sorting complex required for transport III), a complex involved in degradation of surface receptor proteins and formation of endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (MIM 164010), is required for both MVB formation and regulation of cell cycle progression (Tsang et al., 2006 [PubMed 16730941]).[supplied by OMIM, Mar 2008]

CHMP4C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019286573).

BP6

Variant 8-81758536-G-A is Benign according to our data. Variant chr8-81758536-G-A is described in ClinVar as [Benign]. Clinvar id is 1225623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHMP4C	NM_152284.4 linkuse as main transcript	c.694G>A	p.Ala232Thr	missense_variant	5/5	ENST00000297265.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHMP4C	ENST00000297265.5 linkuse as main transcript	c.694G>A	p.Ala232Thr	missense_variant	5/5	1	NM_152284.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0506

AC:

7697

AN:

152088

Hom.:

222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0255

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0453

Gnomad ASJ

AF:

0.0866

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0815

Gnomad FIN

AF:

0.0441

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0676

Gnomad OTH

AF:

0.0516

GnomAD3 exomes

AF:

0.0540

AC:

13565

AN:

250974

Hom.:

443

AF XY:

0.0567

AC XY:

7686

AN XY:

135646

show subpopulations

Gnomad AFR exome

AF:

0.0246

Gnomad AMR exome

AF:

0.0286

Gnomad ASJ exome

AF:

0.0793

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0731

Gnomad FIN exome

AF:

0.0438

Gnomad NFE exome

AF:

0.0691

Gnomad OTH exome

AF:

0.0589

GnomAD4 exome

AF:

0.0646

AC:

94107

AN:

1455872

Hom.:

3327

Cov.:

AF XY:

0.0657

AC XY:

47624

AN XY:

724604

show subpopulations

Gnomad4 AFR exome

AF:

0.0281

Gnomad4 AMR exome

AF:

0.0313

Gnomad4 ASJ exome

AF:

0.0811

Gnomad4 EAS exome

AF:

0.000303

Gnomad4 SAS exome

AF:

0.0740

Gnomad4 FIN exome

AF:

0.0468

Gnomad4 NFE exome

AF:

0.0689

Gnomad4 OTH exome

AF:

0.0649

GnomAD4 genome

AF:

0.0506

AC:

7699

AN:

152206

Hom.:

224

Cov.:

AF XY:

0.0505

AC XY:

3758

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0256

Gnomad4 AMR

AF:

0.0452

Gnomad4 ASJ

AF:

0.0866

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0812

Gnomad4 FIN

AF:

0.0441

Gnomad4 NFE

AF:

0.0676

Gnomad4 OTH

AF:

0.0506

Alfa

AF:

0.0656

Hom.:

592

Bravo

AF:

0.0474

TwinsUK

AF:

0.0696

AC:

258

ALSPAC

AF:

0.0703

AC:

271

ESP6500AA

AF:

0.0300

AC:

132

ESP6500EA

AF:

0.0666

AC:

573

ExAC

AF:

0.0555

AC:

6740

Asia WGS

AF:

0.0290

AC:

103

AN:

3478

EpiCase

AF:

0.0689

EpiControl

AF:

0.0731

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 18, 2019

This variant is associated with the following publications: (PMID: 30181294) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.58

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.27

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.14

MPC

0.11

ClinPred

0.017

GERP RS

6.1

Varity_R

0.83

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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