16-89645998-G-C
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1
The NM_002768.5(CHMP1A):c.*68C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000319 in 1,611,906 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00025 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00033 ( 6 hom. )
Consequence
CHMP1A
NM_002768.5 3_prime_UTR
NM_002768.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.853
Genes affected
CHMP1A (HGNC:8740): (charged multivesicular body protein 1A) This gene encodes a member of the CHMP/Chmp family of proteins which are involved in multivesicular body sorting of proteins to the interiors of lysosomes. The initial prediction of the protein sequence encoded by this gene suggested that the encoded protein was a metallopeptidase. The nomenclature has been updated recently to reflect the correct biological function of this encoded protein. Several transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 16-89645998-G-C is Benign according to our data. Variant chr16-89645998-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2647118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000249 (38/152358) while in subpopulation SAS AF= 0.00745 (36/4832). AF 95% confidence interval is 0.00553. There are 0 homozygotes in gnomad4. There are 29 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHMP1A | NM_002768.5 | c.*68C>G | 3_prime_UTR_variant | 7/7 | ENST00000397901.8 | ||
CHMP1A | NM_001083314.4 | c.639C>G | p.Thr213= | synonymous_variant | 6/6 | ||
CHMP1A | XM_047434195.1 | c.*68C>G | 3_prime_UTR_variant | 7/7 | |||
CHMP1A | NR_046418.3 | n.947C>G | non_coding_transcript_exon_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHMP1A | ENST00000397901.8 | c.*68C>G | 3_prime_UTR_variant | 7/7 | 1 | NM_002768.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000250 AC: 38AN: 152240Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
38
AN:
152240
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000751 AC: 184AN: 245122Hom.: 1 AF XY: 0.000980 AC XY: 131AN XY: 133612
GnomAD3 exomes
AF:
AC:
184
AN:
245122
Hom.:
AF XY:
AC XY:
131
AN XY:
133612
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000326 AC: 476AN: 1459548Hom.: 6 Cov.: 31 AF XY: 0.000459 AC XY: 333AN XY: 726112
GnomAD4 exome
AF:
AC:
476
AN:
1459548
Hom.:
Cov.:
31
AF XY:
AC XY:
333
AN XY:
726112
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000249 AC: 38AN: 152358Hom.: 0 Cov.: 33 AF XY: 0.000389 AC XY: 29AN XY: 74500
GnomAD4 genome
?
AF:
AC:
38
AN:
152358
Hom.:
Cov.:
33
AF XY:
AC XY:
29
AN XY:
74500
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | CHMP1A: BP4, BP7 - |
CHMP1A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 22, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at