Genetic Variant CHMP7:c.1121-14T>C (chr8-23260130-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_152272.5(CHMP7):c.1121-14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,607,370 control chromosomes in the GnomAD database, including 157,041 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 0.34 ( 11225 hom., cov: 32)

Exomes 𝑓: 0.44 ( 145816 hom. )

Consequence

CHMP7
NM_152272.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0850

Publications

12 publications found

Variant links:

Genes affected

CHMP7 (HGNC:28439): (charged multivesicular body protein 7) Involved in several processes, including late endosome to vacuole transport; midbody abscission; and mitotic nuclear division. Located in cytosol; nuclear envelope; and nucleoplasm. Part of ESCRT III complex. Colocalizes with chromatin. [provided by Alliance of Genome Resources, Apr 2022]

CHMP7 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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP7	NM_152272.5 link	c.1121-14T>C		intron_variant	Intron 9 of 10	ENST00000397677.6	NP_689485.1	Q8WUX9-1B3KUH0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP7	ENST00000397677.6 link	c.1121-14T>C		intron_variant	Intron 9 of 10	1	NM_152272.5	ENSP00000380794.1		Q8WUX9-1

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52363

AN:

151978

Hom.:

11224

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.568

Gnomad AMR

AF:

0.398

Gnomad ASJ

AF:

0.575

Gnomad EAS

AF:

0.0379

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.462

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.465

Gnomad OTH

AF:

0.364

GnomAD2 exomes

AF:

0.405

AC:

101508

AN:

250754

AF XY:

0.415

show subpopulations

Gnomad AFR exome

AF:

0.0982

Gnomad AMR exome

AF:

0.418

Gnomad ASJ exome

AF:

0.567

Gnomad EAS exome

AF:

0.0282

Gnomad FIN exome

AF:

0.466

Gnomad NFE exome

AF:

0.469

Gnomad OTH exome

AF:

0.439

GnomAD4 exome

AF:

0.437

AC:

636428

AN:

1455274

Hom.:

145816

Cov.:

AF XY:

0.440

AC XY:

319077

AN XY:

724364

show subpopulations

African (AFR)

AF:

0.0879

AC:

2935

AN:

33406

American (AMR)

AF:

0.420

AC:

18740

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

14895

AN:

26078

East Asian (EAS)

AF:

0.0493

AC:

1956

AN:

39678

South Asian (SAS)

AF:

0.444

AC:

38243

AN:

86094

European-Finnish (FIN)

AF:

0.468

AC:

24978

AN:

53338

Middle Eastern (MID)

AF:

0.479

AC:

2757

AN:

5750

European-Non Finnish (NFE)

AF:

0.458

AC:

507043

AN:

1106092

Other (OTH)

AF:

0.413

AC:

24881

AN:

60172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

16735

33470

50204

66939

83674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14718

29436

44154

58872

73590

<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:

0.344

AC:

52363

AN:

152096

Hom.:

11225

Cov.:

AF XY:

0.344

AC XY:

25582

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.102

AC:

4245

AN:

41518

American (AMR)

AF:

0.399

AC:

6094

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.575

AC:

1993

AN:

3468

East Asian (EAS)

AF:

0.0381

AC:

198

AN:

5192

South Asian (SAS)

AF:

0.413

AC:

1987

AN:

4814

European-Finnish (FIN)

AF:

0.462

AC:

4863

AN:

10528

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.465

AC:

31578

AN:

67970

Other (OTH)

AF:

0.360

AC:

761

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1574

3148

4721

6295

7869

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<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:

0.404

Hom.:

21450

Bravo

AF:

0.326

Asia WGS

AF:

0.233

AC:

814

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.3

(source)

DANN

Benign

0.43

PhyloP100

-0.085

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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