chr20-33848172-C-T

Variant names:

• chr20-33848172-C-T
• rs7274168
• NM_176812.5:c.191-295C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_176812.5(CHMP4B):​c.191-295C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,842 control chromosomes in the GnomAD database, including 20,894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (20894 hom., cov: 31)
• Consequence: CHMP4B NM_176812.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0350
• Publications: 11 publications found

Genes affected

CHMP4B (HGNC:16171): (charged multivesicular body protein 4B) This gene encodes a member of the chromatin-modifying protein/charged multivesicular body protein (CHMP) protein family. The protein is part of the endosomal sorting complex required for transport (ESCRT) complex III (ESCRT-III), which functions in the sorting of endocytosed cell-surface receptors into multivesicular endosomes. The ESCRT machinery also functions in the final abscisson stage of cytokinesis and in the budding of enveloped viruses such as HIV-1. The three proteins of the CHMP4 subfamily interact with programmed cell death 6 interacting protein (PDCD6IP, also known as ALIX), which also functions in the ESCRT pathway. The CHMP4 proteins assemble into membrane-attached 5-nm filaments that form circular scaffolds and promote or stabilize outward budding. These polymers are proposed to help generate the luminal vesicles of multivesicular bodies. Mutations in this gene result in autosomal dominant posterior polar cataracts.[provided by RefSeq, Oct 2009]

CHMP4B Gene-Disease associations (from GenCC):

• cataract 31 multiple types

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• early-onset posterior polar cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• early-onset posterior subcapsular cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-33848172-C-T is Benign according to our data. Variant chr20-33848172-C-T is described in ClinVar as [Benign]. Clinvar id is 1180415.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP4B	NM_176812.5	c.191-295C>T		intron_variant	Intron 1 of 4	ENST00000217402.3	NP_789782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP4B	ENST00000217402.3	c.191-295C>T		intron_variant	Intron 1 of 4	1	NM_176812.5	ENSP00000217402.2

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77763 AN: 151724 Hom.: 20886 Cov.: 31

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.571

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.512 AC: 77799 AN: 151842 Hom.: 20894 Cov.: 31 AF XY: 0.524 AC XY: 38871 AN XY: 74234

African (AFR) AF: 0.382 AC: 15795 AN: 41376

American (AMR) AF: 0.564 AC: 8605 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2127 AN: 3466

East Asian (EAS) AF: 0.904 AC: 4661 AN: 5158

South Asian (SAS) AF: 0.618 AC: 2964 AN: 4800

European-Finnish (FIN) AF: 0.637 AC: 6716 AN: 10548

Middle Eastern (MID) AF: 0.716 AC: 209 AN: 292

European-Non Finnish (NFE) AF: 0.516 AC: 35042 AN: 67922

Other (OTH) AF: 0.570 AC: 1202 AN: 2108

Alfa AF: 0.513 Hom.: 8986

Bravo AF: 0.504

Asia WGS AF: 0.691 AC: 2400 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 21, 2018

GeneDx

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	-0.89
CADD	Benign	3.2
DANN	Benign	0.70
PhyloP100		0.035
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7274168; hg19: chr20-32435978;