rs61745250
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_133459.4(CCBE1):c.837C>T(p.Pro279=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,614,160 control chromosomes in the GnomAD database, including 252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.011 ( 17 hom., cov: 33)
Exomes 𝑓: 0.016 ( 235 hom. )
Consequence
CCBE1
NM_133459.4 synonymous
NM_133459.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.36
Genes affected
CCBE1 (HGNC:29426): (collagen and calcium binding EGF domains 1) This gene is thought to function in extracellular matrix remodeling and migration. It is predominantly expressed in the ovary, but down regulated in ovarian cancer cell lines and primary carcinomas, suggesting its role as a tumour suppressor. Mutations in this gene have been associated with Hennekam lymphangiectasia-lymphedema syndrome, a generalized lymphatic dysplasia in humans. [provided by RefSeq, Mar 2010]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
Variant 18-59439755-G-A is Benign according to our data. Variant chr18-59439755-G-A is described in ClinVar as [Benign]. Clinvar id is 262356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-59439755-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.36 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0115 (1751/152328) while in subpopulation NFE AF= 0.0191 (1297/68026). AF 95% confidence interval is 0.0182. There are 17 homozygotes in gnomad4. There are 824 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 17 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCBE1 | NM_133459.4 | c.837C>T | p.Pro279= | synonymous_variant | 8/11 | ENST00000439986.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCBE1 | ENST00000439986.9 | c.837C>T | p.Pro279= | synonymous_variant | 8/11 | 1 | NM_133459.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0115 AC: 1753AN: 152210Hom.: 17 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
1753
AN:
152210
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: 0.0121 AC: 3026AN: 250740Hom.: 35 AF XY: 0.0120 AC XY: 1635AN XY: 135762
GnomAD3 exomes
AF:
AC:
3026
AN:
250740
Hom.:
AF XY:
AC XY:
1635
AN XY:
135762
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: 0.0163 AC: 23898AN: 1461832Hom.: 235 Cov.: 32 AF XY: 0.0158 AC XY: 11526AN XY: 727216
GnomAD4 exome
AF:
AC:
23898
AN:
1461832
Hom.:
Cov.:
32
AF XY:
AC XY:
11526
AN XY:
727216
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: 0.0115 AC: 1751AN: 152328Hom.: 17 Cov.: 33 AF XY: 0.0111 AC XY: 824AN XY: 74496
GnomAD4 genome
?
AF:
AC:
1751
AN:
152328
Hom.:
Cov.:
33
AF XY:
AC XY:
824
AN XY:
74496
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:
Asia WGS
AF:
AC:
6
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hennekam lymphangiectasia-lymphedema syndrome 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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