20-33811394-C-G

Variant names:

• chr20-33811394-C-G
• rs2626522
• NM_176812.5:c.-75C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0180
• Publications: 9 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]

ZNF341-AS1 (HGNC:50736): (ZNF341 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
CHMP4B	NM_176812.5	c.-75C>G		5_prime_UTR_variant	Exon 1 of 5	ENST00000217402.3	NP_789782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP4B	ENST00000217402.3	c.-75C>G		5_prime_UTR_variant	Exon 1 of 5	1	NM_176812.5	ENSP00000217402.2
ZNF341-AS1	ENST00000824838.1	n.259+669G>C		intron_variant	Intron 1 of 3
ZNF341-AS1	ENST00000443171.7	n.-247G>C		upstream_gene_variant		2

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

African (AFR) AF: 0.365 AC: 7885 AN: 21578

American (AMR) AF: 0.587 AC: 4632 AN: 7894

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 7764 AN: 13802

East Asian (EAS) AF: 0.912 AC: 23067 AN: 25292

South Asian (SAS) AF: 0.558 AC: 17437 AN: 31230

European-Finnish (FIN) AF: 0.582 AC: 18183 AN: 31246

Middle Eastern (MID) AF: 0.621 AC: 1795 AN: 2892

European-Non Finnish (NFE) AF: 0.459 AC: 415116 AN: 905234

Other (OTH) AF: 0.501 AC: 21690 AN: 43298

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

African (AFR) AF: 0.371 AC: 15210 AN: 41034

American (AMR) AF: 0.542 AC: 8209 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 1976 AN: 3426

East Asian (EAS) AF: 0.904 AC: 4546 AN: 5026

South Asian (SAS) AF: 0.569 AC: 2706 AN: 4756

European-Finnish (FIN) AF: 0.574 AC: 5904 AN: 10286

Middle Eastern (MID) AF: 0.664 AC: 190 AN: 286

European-Non Finnish (NFE) AF: 0.483 AC: 32282 AN: 66870

Other (OTH) AF: 0.545 AC: 1128 AN: 2068

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.55
CADD	Benign	17
DANN	Benign	0.73
PhyloP100		-0.018
PromoterAI		-0.034	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2626522; hg19: chr20-32399200;