rs1044499

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_014043.4(CHMP2B):c.372A>C(p.Thr124Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0836 in 1,604,988 control chromosomes in the GnomAD database, including 6,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 714 hom., cov: 32)

Exomes 𝑓: 0.083 ( 5777 hom. )

Consequence

CHMP2B
NM_014043.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: 0.606

Variant links:

Genes affected

CHMP2B (HGNC:24537): (charged multivesicular body protein 2B) This gene encodes a component of the heteromeric ESCRT-III complex (Endosomal Sorting Complex Required for Transport III) that functions in the recycling or degradation of cell surface receptors. ESCRT-III functions in the concentration and invagination of ubiquitinated endosomal cargos into intralumenal vesicles. The protein encoded by this gene is found as a monomer in the cytosol or as an oligomer in ESCRT-III complexes on endosomal membranes. It is expressed in neurons of all major regions of the brain. Mutations in this gene result in one form of familial frontotemporal lobar degeneration. [provided by RefSeq, Jul 2008]

CHMP2B 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 (BayesDel_noAF=-0.53).

BP6

Variant 3-87249925-A-C is Benign according to our data. Variant chr3-87249925-A-C is described in ClinVar as [Benign]. Clinvar id is 98001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-87249925-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP2B	NM_014043.4 link	c.372A>C	p.Thr124Thr	synonymous_variant	Exon 4 of 6	ENST00000263780.9	NP_054762.2	Q9UQN3-1B2RE76
CHMP2B	NM_001410777.1 link	c.468A>C	p.Thr156Thr	synonymous_variant	Exon 5 of 7		NP_001397706.1
CHMP2B	NM_001244644.2 link	c.249A>C	p.Thr83Thr	synonymous_variant	Exon 3 of 5		NP_001231573.1	Q9UQN3-2B2RE76
CHMP2B	XM_011533576.3 link	c.420A>C	p.Thr140Thr	synonymous_variant	Exon 4 of 6		XP_011531878.1	A0A087WW88

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP2B	ENST00000263780.9 link	c.372A>C	p.Thr124Thr	synonymous_variant	Exon 4 of 6	1	NM_014043.4	ENSP00000263780.4		Q9UQN3-1

Frequencies

GnomAD3 genomes

AF:

0.0916

AC:

13920

AN:

151946

Hom.:

711

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.0813

Gnomad FIN

AF:

0.0474

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.0810

Gnomad OTH

AF:

0.0952

GnomAD3 exomes

AF:

0.0945

AC:

23558

AN:

249392

Hom.:

1386

AF XY:

0.0934

AC XY:

12589

AN XY:

134788

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.111

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.204

Gnomad SAS exome

AF:

0.0837

Gnomad FIN exome

AF:

0.0471

Gnomad NFE exome

AF:

0.0795

Gnomad OTH exome

AF:

0.0983

GnomAD4 exome

AF:

0.0827

AC:

120176

AN:

1452922

Hom.:

5777

Cov.:

AF XY:

0.0833

AC XY:

60202

AN XY:

722730

show subpopulations

Gnomad4 AFR exome

AF:

0.109

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.235

Gnomad4 SAS exome

AF:

0.0834

Gnomad4 FIN exome

AF:

0.0491

Gnomad4 NFE exome

AF:

0.0754

Gnomad4 OTH exome

AF:

0.0945

GnomAD4 genome

AF:

0.0916

AC:

13936

AN:

152066

Hom.:

714

Cov.:

AF XY:

0.0910

AC XY:

6763

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0998

Gnomad4 ASJ

AF:

0.120

Gnomad4 EAS

AF:

0.199

Gnomad4 SAS

AF:

0.0801

Gnomad4 FIN

AF:

0.0474

Gnomad4 NFE

AF:

0.0810

Gnomad4 OTH

AF:

0.0952

Alfa

AF:

0.0873

Hom.:

1287

Bravo

AF:

0.0974

Asia WGS

AF:

0.144

AC:

500

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2Other:1

Aug 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

VIB Department of Molecular Genetics, University of Antwerp

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Frontotemporal dementia and/or amyotrophic lateral sclerosis 7

Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.5

DANN

Benign

0.69

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