Genetic Variant NM_024591.5: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.

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.*948C>G		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.*948C>G	3_prime_UTR	Exon 8 of 8	ENSP00000317468.5	Q96FZ7
CHMP6	ENST00000571457.1	TSL:3	c.424+1681C>G	intron	N/A	ENSP00000461238.1	I3L4G8
ENSG00000263218	ENST00000576215.1	TSL:3	n.30G>C	non_coding_transcript_exon	Exon 1 of 2

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over