Genetic Variant NM_024591.5: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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024591.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHMP6	NM_024591.5	MANE Select	c.*521T>C		3_prime_UTR	Exon 8 of 8	NP_078867.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHMP6	ENST00000325167.9	TSL:1 MANE Select	c.*521T>C	3_prime_UTR	Exon 8 of 8	ENSP00000317468.5	Q96FZ7
CHMP6	ENST00000571457.1	TSL:3	c.424+1254T>C	intron	N/A	ENSP00000461238.1	I3L4G8
ENSG00000263218	ENST00000576215.1	TSL:3	n.305-132A>G	intron	N/A

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over