Genetic Variant CHMP5:c.222-142A>G (chr9-33270481-A-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_016410.6(CHMP5):c.222-142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 643,054 control chromosomes in the GnomAD database, including 172,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.64 ( 34382 hom., cov: 32)

Exomes 𝑓: 0.75 ( 137920 hom. )

Consequence

CHMP5
NM_016410.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.967

Publications

7 publications found

Variant links:

Genes affected

CHMP5 (HGNC:26942): (charged multivesicular body protein 5) CHMP5 belongs to the chromatin-modifying protein/charged multivesicular body protein (CHMP) family. These proteins are components of ESCRT-III (endosomal sorting complex required for transport III), a complex involved in degradation of surface receptor proteins and formation of endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (MIM 164010), is required for both MVB formation and regulation of cell cycle progression (Tsang et al., 2006 [PubMed 16730941]).[supplied by OMIM, Mar 2008]

CHMP5 links:

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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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016410.6. 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
	CHMP5	NM_016410.6	MANE Select	c.222-142A>G		intron	N/A	NP_057494.3
	CHMP5	NM_001195536.2		c.222-142A>G		intron	N/A	NP_001182465.1	Q9NZZ3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHMP5	ENST00000223500.9	TSL:1 MANE Select	c.222-142A>G	intron	N/A	ENSP00000223500.7	Q9NZZ3-1
CHMP5	ENST00000937845.1		c.261-142A>G	intron	N/A	ENSP00000607904.1
CHMP5	ENST00000948350.1		c.249-142A>G	intron	N/A	ENSP00000618409.1

Frequencies

GnomAD3 genomes

AF:

0.645

AC:

97923

AN:

151792

Hom.:

34380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.903

Gnomad AMR

AF:

0.706

Gnomad ASJ

AF:

0.764

Gnomad EAS

AF:

0.743

Gnomad SAS

AF:

0.716

Gnomad FIN

AF:

0.785

Gnomad MID

AF:

0.691

Gnomad NFE

AF:

0.773

Gnomad OTH

AF:

0.667

GnomAD4 exome

AF:

0.745

AC:

366048

AN:

491146

Hom.:

137920

AF XY:

0.745

AC XY:

193445

AN XY:

259544

show subpopulations

African (AFR)

AF:

0.328

AC:

4094

AN:

12470

American (AMR)

AF:

0.732

AC:

12460

AN:

17028

Ashkenazi Jewish (ASJ)

AF:

0.759

AC:

10511

AN:

13854

East Asian (EAS)

AF:

0.710

AC:

21699

AN:

30572

South Asian (SAS)

AF:

0.736

AC:

33152

AN:

45050

European-Finnish (FIN)

AF:

0.777

AC:

31571

AN:

40638

Middle Eastern (MID)

AF:

0.727

AC:

1600

AN:

2200

European-Non Finnish (NFE)

AF:

0.765

AC:

231494

AN:

302428

Other (OTH)

AF:

0.724

AC:

19467

AN:

26906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

4276

8551

12827

17102

21378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1494

2988

4482

5976

7470

<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:

0.645

AC:

97946

AN:

151908

Hom.:

34382

Cov.:

AF XY:

0.650

AC XY:

48268

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.337

AC:

13945

AN:

41326

American (AMR)

AF:

0.706

AC:

10793

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.764

AC:

2650

AN:

3470

East Asian (EAS)

AF:

0.743

AC:

3838

AN:

5168

South Asian (SAS)

AF:

0.717

AC:

3458

AN:

4824

European-Finnish (FIN)

AF:

0.785

AC:

8294

AN:

10566

Middle Eastern (MID)

AF:

0.682

AC:

199

AN:

292

European-Non Finnish (NFE)

AF:

0.773

AC:

52536

AN:

67958

Other (OTH)

AF:

0.668

AC:

1411

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1518

3037

4555

6074

7592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

778

1556

2334

3112

3890

<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:

0.683

Hom.:

4444

Bravo

AF:

0.625

Asia WGS

AF:

0.668

AC:

2325

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.012

(source)

DANN

Benign

0.66

PhyloP100

-0.97

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