dbSNP rs844239: 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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:

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=-0.81).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP5	NM_016410.6 link	c.222-142A>G		intron_variant	Intron 3 of 7	ENST00000223500.9	NP_057494.3	Q9NZZ3-1
CHMP5	NM_001195536.2 link	c.222-142A>G		intron_variant	Intron 3 of 6		NP_001182465.1	Q9NZZ3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP5	ENST00000223500.9 link	c.222-142A>G		intron_variant	Intron 3 of 7	1	NM_016410.6	ENSP00000223500.7		Q9NZZ3-1
CHMP5	ENST00000419016.6 link	c.222-142A>G		intron_variant	Intron 3 of 6	2		ENSP00000442725.1		Q9NZZ3-2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over