chr3-87227549-C-T

Position:

chr3-87227549-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014043.4(CHMP2B):c.27C>T(p.Thr9=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0845 in 1,614,034 control chromosomes in the GnomAD database, including 6,606 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 731 hom., cov: 32)

Exomes 𝑓: 0.084 ( 5875 hom. )

Consequence

CHMP2B
NM_014043.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.155

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 3-87227549-C-T is Benign according to our data. Variant chr3-87227549-C-T is described in ClinVar as [Benign]. Clinvar id is 97999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-87227549-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.155 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CHMP2B	NM_014043.4 linkuse as main transcript	c.27C>T	p.Thr9=	synonymous_variant	1/6	ENST00000263780.9	NP_054762.2
CHMP2B	NM_001244644.2 linkuse as main transcript	c.-5C>T		5_prime_UTR_variant	1/5		NP_001231573.1
CHMP2B	NM_001410777.1 linkuse as main transcript	c.-5C>T		5_prime_UTR_variant	1/7		NP_001397706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHMP2B	ENST00000263780.9 linkuse as main transcript	c.27C>T	p.Thr9=	synonymous_variant	1/6	1	NM_014043.4	ENSP00000263780	P1	Q9UQN3-1

Frequencies

GnomAD3 genomes

AF:

0.0927

AC:

14100

AN:

152078

Hom.:

727

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.0815

Gnomad FIN

AF:

0.0474

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.0810

Gnomad OTH

AF:

0.0961

GnomAD3 exomes

AF:

0.0948

AC:

23734

AN:

250234

Hom.:

1401

AF XY:

0.0937

AC XY:

12679

AN XY:

135316

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.112

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.204

Gnomad SAS exome

AF:

0.0836

Gnomad FIN exome

AF:

0.0470

Gnomad NFE exome

AF:

0.0796

Gnomad OTH exome

AF:

0.0983

GnomAD4 exome

AF:

0.0837

AC:

122286

AN:

1461838

Hom.:

5875

Cov.:

AF XY:

0.0842

AC XY:

61226

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.235

Gnomad4 SAS exome

AF:

0.0839

Gnomad4 FIN exome

AF:

0.0493

Gnomad4 NFE exome

AF:

0.0763

Gnomad4 OTH exome

AF:

0.0957

GnomAD4 genome

AF:

0.0928

AC:

14123

AN:

152196

Hom.:

731

Cov.:

AF XY:

0.0922

AC XY:

6861

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.108

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.120

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.0804

Gnomad4 FIN

AF:

0.0474

Gnomad4 NFE

AF:

0.0810

Gnomad4 OTH

AF:

0.0960

Alfa

AF:

0.0869

Hom.:

937

Bravo

AF:

0.0986

Asia WGS

AF:

0.145

AC:

502

AN:

3478

EpiCase

AF:

0.0887

EpiControl

AF:

0.0877

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	literature only	VIB Department of Molecular Genetics, University of Antwerp	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	- -

Frontotemporal dementia and/or amyotrophic lateral sclerosis 7

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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