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GeneBe

17-80999102-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_024591.5(CHMP6):c.555C>T(p.Asn185=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00462 in 1,614,024 control chromosomes in the GnomAD database, including 319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.025 ( 168 hom., cov: 34)
Exomes 𝑓: 0.0025 ( 151 hom. )

Consequence

CHMP6
NM_024591.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.235
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-80999102-C-T is Benign according to our data. Variant chr17-80999102-C-T is described in ClinVar as [Benign]. Clinvar id is 777256.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.235 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0838 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CHMP6NM_024591.5 linkuse as main transcriptc.555C>T p.Asn185= synonymous_variant 8/8 ENST00000325167.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CHMP6ENST00000325167.9 linkuse as main transcriptc.555C>T p.Asn185= synonymous_variant 8/81 NM_024591.5 P1
CHMP6ENST00000572525.5 linkuse as main transcriptc.297C>T p.Asn99= synonymous_variant 8/83
CHMP6ENST00000571457.1 linkuse as main transcriptc.424+682C>T intron_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0245
AC:
3733
AN:
152238
Hom.:
167
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0861
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00759
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.0129
GnomAD3 exomes
AF:
0.00637
AC:
1598
AN:
251032
Hom.:
77
AF XY:
0.00465
AC XY:
631
AN XY:
135752
show subpopulations
Gnomad AFR exome
AF:
0.0872
Gnomad AMR exome
AF:
0.00396
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000185
Gnomad OTH exome
AF:
0.00261
GnomAD4 exome
AF:
0.00254
AC:
3709
AN:
1461668
Hom.:
151
Cov.:
32
AF XY:
0.00212
AC XY:
1542
AN XY:
727158
show subpopulations
Gnomad4 AFR exome
AF:
0.0908
Gnomad4 AMR exome
AF:
0.00432
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000232
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000827
Gnomad4 OTH exome
AF:
0.00565
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0246
AC:
3743
AN:
152356
Hom.:
168
Cov.:
34
AF XY:
0.0232
AC XY:
1732
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.0861
Gnomad4 AMR
AF:
0.00758
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.0128
Alfa
AF:
0.0118
Hom.:
54
Bravo
AF:
0.0267
Asia WGS
AF:
0.00549
AC:
19
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeOct 19, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
Cadd
Benign
3.9
Dann
Benign
0.89
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35687235; hg19: chr17-78972902; API