Genetic Variant CHMP6:c.*948C>G (chr17-81000101-C-G) – 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.*948C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,118 control chromosomes in the GnomAD database, including 11,184 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 0.38 ( 11183 hom., cov: 33)

Exomes 𝑓: 0.33 ( 1 hom. )

Consequence

CHMP6
NM_024591.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.550

Publications

7 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=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP6	NM_024591.5 link	c.*948C>G		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.*948C>G	3_prime_UTR_variant	Exon 8 of 8	1	NM_024591.5	ENSP00000317468.5	Q96FZ7
ENSG00000263218	ENST00000576215.1 link	n.30G>C	non_coding_transcript_exon_variant	Exon 1 of 2	3
ENSG00000263218	ENST00000577061.2 link	n.27G>C	non_coding_transcript_exon_variant	Exon 1 of 2	3
CHMP6	ENST00000571457.1 link	c.424+1681C>G	intron_variant	Intron 6 of 6	3		ENSP00000461238.1	I3L4G8

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

57191

AN:

151966

Hom.:

11178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.667

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.392

Gnomad SAS

AF:

0.339

Gnomad FIN

AF:

0.340

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.424

Gnomad OTH

AF:

0.375

GnomAD4 exome

AF:

0.333

AC:

AN:

Hom.:

Cov.:

AF XY:

0.300

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

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:

0.376

AC:

57231

AN:

152088

Hom.:

11183

Cov.:

AF XY:

0.372

AC XY:

27682

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.276

AC:

11467

AN:

41492

American (AMR)

AF:

0.452

AC:

6916

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.372

AC:

1291

AN:

3468

East Asian (EAS)

AF:

0.391

AC:

2017

AN:

5156

South Asian (SAS)

AF:

0.339

AC:

1633

AN:

4822

European-Finnish (FIN)

AF:

0.340

AC:

3595

AN:

10588

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.424

AC:

28833

AN:

67960

Other (OTH)

AF:

0.375

AC:

792

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1848

3695

5543

7390

9238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.257

Hom.:

628

Bravo

AF:

0.384

Asia WGS

AF:

0.356

AC:

1241

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.62

(source)

DANN

Benign

0.44

PhyloP100

-0.55

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