Genetic Variant CHMP6:c.*521T>C (chr17-80999674-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024591.5(CHMP6):c.*521T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 154,150 control chromosomes in the GnomAD database, including 10,020 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 9865 hom., cov: 33)

Exomes 𝑓: 0.37 ( 155 hom. )

Consequence

CHMP6
NM_024591.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.29

Publications

14 publications found

Variant links:

Genes affected

CHMP6 (HGNC:25675): (charged multivesicular body protein 6) This gene encodes a member of the chromatin-modifying protein/charged multivesicular body protein family. Proteins in this family are part of the ESCRT-III (endosomal sorting complex required for transport III) which degrades surface receptors, and in biosynthesis of endosomes. [provided by RefSeq, Mar 2012]

CHMP6 links:

ENSG00000263218 (HGNC:):

ENSG00000263218 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP6	NM_024591.5 link	c.*521T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000325167.9	NP_078867.2	Q96FZ7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHMP6	ENST00000325167.9 link	c.*521T>C	3_prime_UTR_variant	Exon 8 of 8	1	NM_024591.5	ENSP00000317468.5	Q96FZ7
CHMP6	ENST00000571457.1 link	c.424+1254T>C	intron_variant	Intron 6 of 6	3		ENSP00000461238.1	I3L4G8
ENSG00000263218	ENST00000576215.1 link	n.305-132A>G	intron_variant	Intron 1 of 1	3
ENSG00000263218	ENST00000577061.2 link	n.144-15A>G	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.335

AC:

50937

AN:

152076

Hom.:

9863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.667

Gnomad AMR

AF:

0.434

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.393

Gnomad SAS

AF:

0.342

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.349

GnomAD4 exome

AF:

0.371

AC:

725

AN:

1954

Hom.:

155

Cov.:

AF XY:

0.347

AC XY:

346

AN XY:

996

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.420

AC:

AN:

176

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

AN:

East Asian (EAS)

AF:

0.269

AC:

AN:

South Asian (SAS)

AF:

0.278

AC:

AN:

158

European-Finnish (FIN)

AF:

0.342

AC:

AN:

Middle Eastern (MID)

AF:

0.300

AC:

AN:

European-Non Finnish (NFE)

AF:

0.393

AC:

552

AN:

1404

Other (OTH)

AF:

0.302

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.335

AC:

50949

AN:

152196

Hom.:

9865

Cov.:

AF XY:

0.332

AC XY:

24698

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.129

AC:

5363

AN:

41552

American (AMR)

AF:

0.435

AC:

6645

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

1282

AN:

3470

East Asian (EAS)

AF:

0.393

AC:

2029

AN:

5164

South Asian (SAS)

AF:

0.341

AC:

1643

AN:

4814

European-Finnish (FIN)

AF:

0.345

AC:

3655

AN:

10592

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.425

AC:

28910

AN:

67994

Other (OTH)

AF:

0.349

AC:

737

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1675

3351

5026

6702

8377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

492

984

1476

1968

2460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.410

Hom.:

15741

Bravo

AF:

0.335

Asia WGS

AF:

0.348

AC:

1213

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.6

(source)

DANN

Benign

0.32

PhyloP100

-4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over