rs1421
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002354.3(EPCAM):c.*118T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 794,348 control chromosomes in the GnomAD database, including 6,859 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.10 ( 1096 hom., cov: 33)
Exomes 𝑓: 0.13 ( 5763 hom. )
Consequence
EPCAM
NM_002354.3 3_prime_UTR
NM_002354.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0870
Genes affected
EPCAM (HGNC:11529): (epithelial cell adhesion molecule) This gene encodes a carcinoma-associated antigen and is a member of a family that includes at least two type I membrane proteins. This antigen is expressed on most normal epithelial cells and gastrointestinal carcinomas and functions as a homotypic calcium-independent cell adhesion molecule. The antigen is being used as a target for immunotherapy treatment of human carcinomas. Mutations in this gene result in congenital tufting enteropathy. [provided by RefSeq, Dec 2008]
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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=-0.77).
BP6
?
Variant 2-47386731-T-C is Benign according to our data. Variant chr2-47386731-T-C is described in ClinVar as [Benign]. Clinvar id is 1275848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47386731-T-C is described in Lovd as [Benign]. Variant chr2-47386731-T-C is described in Lovd as [Likely_benign]. Variant chr2-47386731-T-C is described in Lovd as [Pathogenic].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPCAM | NM_002354.3 | c.*118T>C | 3_prime_UTR_variant | 9/9 | ENST00000263735.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPCAM | ENST00000263735.9 | c.*118T>C | 3_prime_UTR_variant | 9/9 | 1 | NM_002354.3 | P1 | ||
EPCAM | ENST00000405271.5 | c.*118T>C | 3_prime_UTR_variant | 10/10 | 5 | ||||
EPCAM | ENST00000456133.5 | c.*118T>C | 3_prime_UTR_variant, NMD_transcript_variant | 10/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.104 AC: 15822AN: 152142Hom.: 1098 Cov.: 33
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GnomAD4 exome AF: 0.126 AC: 80730AN: 642088Hom.: 5763 Cov.: 9 AF XY: 0.123 AC XY: 42268AN XY: 343418
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 14, 2018 | This variant is associated with the following publications: (PMID: 30461124) - |
EPCAM-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 04, 2022 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jan 30, 2020 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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