dbSNP rs760790780: CHMP7:p.Pro22His (chr8-23246760-C-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_152272.5(CHMP7):c.65C>A(p.Pro22His) variant causes a missense change. The variant allele was found at a frequency of 0.0000064 in 1,405,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P22L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

CHMP7
NM_152272.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.80

Publications

0 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33152187).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152272.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHMP7	NM_152272.5	MANE Select	c.65C>A	p.Pro22His	missense	Exon 2 of 11	NP_689485.1	Q8WUX9-1
CHMP7	NM_001363183.2		c.65C>A	p.Pro22His	missense	Exon 1 of 9	NP_001350112.1
CHMP7	NM_001317899.2		c.-96C>A		5_prime_UTR	Exon 1 of 10	NP_001304828.1	B3KRZ9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHMP7	ENST00000397677.6	TSL:1 MANE Select	c.65C>A	p.Pro22His	missense	Exon 2 of 11	ENSP00000380794.1	Q8WUX9-1
CHMP7	ENST00000313219.8	TSL:1	c.65C>A	p.Pro22His	missense	Exon 1 of 10	ENSP00000324491.7	Q8WUX9-1
CHMP7	ENST00000880275.1		c.65C>A	p.Pro22His	missense	Exon 2 of 11	ENSP00000550334.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000244

AC:

AN:

163642

AF XY:

0.0000114

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000787

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000153

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.00000640

AC:

AN:

1405536

Hom.:

Cov.:

AF XY:

0.00000576

AC XY:

AN XY:

694070

show subpopulations

African (AFR)

AF:

0.0000314

AC:

AN:

31832

American (AMR)

AF:

0.0000551

AC:

AN:

36330

Ashkenazi Jewish (ASJ)

AF:

0.0000396

AC:

AN:

25264

East Asian (EAS)

AF:

0.00

AC:

AN:

36110

South Asian (SAS)

AF:

0.00

AC:

AN:

79836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5286

European-Non Finnish (NFE)

AF:

0.00000369

AC:

AN:

1083206

Other (OTH)

AF:

0.0000172

AC:

AN:

58238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000256

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.76

M_CAP

Benign

0.031

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.32

MutationAssessor

Benign

1.8

PhyloP100

3.8

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-2.1

REVEL

Benign

0.15

Sift

Uncertain

0.0080

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.52

MutPred

0.32

Loss of catalytic residue at P21 (P = 0.0131)

MVP

0.51

MPC

0.71

ClinPred

0.69

GERP RS

5.8

PromoterAI

-0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.49

gMVP

0.51

Mutation Taster

=43/57

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over