chr20-33848546-G-A
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_176812.5(CHMP4B):c.270G>A(p.Glu90=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000189 in 1,614,222 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 2 hom. )
Consequence
CHMP4B
NM_176812.5 synonymous
NM_176812.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.76
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
Variant 20-33848546-G-A is Benign according to our data. Variant chr20-33848546-G-A is described in ClinVar as [Benign]. Clinvar id is 2188536.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=2.76 with no splicing effect.
BS2
High AC in GnomAd4 at 47 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHMP4B | NM_176812.5 | c.270G>A | p.Glu90= | synonymous_variant | 2/5 | ENST00000217402.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHMP4B | ENST00000217402.3 | c.270G>A | p.Glu90= | synonymous_variant | 2/5 | 1 | NM_176812.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000309 AC: 47AN: 152216Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000585 AC: 147AN: 251430Hom.: 1 AF XY: 0.000545 AC XY: 74AN XY: 135904
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GnomAD4 exome AF: 0.000176 AC: 258AN: 1461888Hom.: 2 Cov.: 32 AF XY: 0.000158 AC XY: 115AN XY: 727248
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GnomAD4 genome AF: 0.000309 AC: 47AN: 152334Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24AN XY: 74484
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cataract 31 multiple types Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | - - |
Computational scores
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Benign
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at