20-33811394-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_176812.5(CHMP4B):c.-75C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 1,232,268 control chromosomes in the GnomAD database, including 146,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (18459 hom., cov: 29)
  • Exomes 𝑓: 0.48 (128250 hom.)
• Consequence: CHMP4B NM_176812.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0180

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 20-33811394-C-G is Benign according to our data. Variant chr20-33811394-C-G is described in ClinVar as [Benign]. Clinvar id is 1240673.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHMP4B	NM_176812.5	c.-75C>G		5_prime_UTR_variant	1/5	ENST00000217402.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHMP4B	ENST00000217402.3	c.-75C>G		5_prime_UTR_variant	1/5	1	NM_176812.5	P1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 72585 AN: 149704 Hom.: 18460 Cov.: 29

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.546

GnomAD4 exome AF: 0.478 AC: 517569 AN: 1082466 Hom.: 128250 Cov.: 17 AF XY: 0.481 AC XY: 249718 AN XY: 519132

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.587

Gnomad4 ASJ exome AF: 0.563

Gnomad4 EAS exome AF: 0.912

Gnomad4 SAS exome AF: 0.558

Gnomad4 FIN exome AF: 0.582

Gnomad4 NFE exome AF: 0.459

Gnomad4 OTH exome AF: 0.501

GnomAD4 genome AF: 0.485 AC: 72604 AN: 149802 Hom.: 18459 Cov.: 29 AF XY: 0.495 AC XY: 36189 AN XY: 73062

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.904

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.545

Alfa AF: 0.463 Hom.: 2023

Bravo AF: 0.481

Asia WGS AF: 0.655 AC: 2203 AN: 3366

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	17
Dann	Benign	0.73

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

Other links and lift over

dbSNP: rs2626522; hg19: chr20-32399200;