rs72958116
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_133459.4(CCBE1):c.*14C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,603,590 control chromosomes in the GnomAD database, including 161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0095 ( 14 hom., cov: 32)
Exomes 𝑓: 0.012 ( 147 hom. )
Consequence
CCBE1
NM_133459.4 3_prime_UTR
NM_133459.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.314
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 18-59435894-G-A is Benign according to our data. Variant chr18-59435894-G-A is described in ClinVar as [Benign]. Clinvar id is 262349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-59435894-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00945 (1439/152214) while in subpopulation SAS AF= 0.0177 (85/4802). AF 95% confidence interval is 0.0147. There are 14 homozygotes in gnomad4. There are 675 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 14 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCBE1 | NM_133459.4 | c.*14C>T | 3_prime_UTR_variant | 11/11 | ENST00000439986.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCBE1 | ENST00000439986.9 | c.*14C>T | 3_prime_UTR_variant | 11/11 | 1 | NM_133459.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00944 AC: 1436AN: 152096Hom.: 13 Cov.: 32
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GnomAD3 exomes AF: 0.0101 AC: 2533AN: 250470Hom.: 28 AF XY: 0.0110 AC XY: 1484AN XY: 135450
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GnomAD4 exome AF: 0.0123 AC: 17829AN: 1451376Hom.: 147 Cov.: 27 AF XY: 0.0125 AC XY: 9025AN XY: 722838
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GnomAD4 genome ? AF: 0.00945 AC: 1439AN: 152214Hom.: 14 Cov.: 32 AF XY: 0.00907 AC XY: 675AN XY: 74434
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Hennekam lymphangiectasia-lymphedema syndrome 1 Benign:1
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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at