rs878854492
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_002354.3(EPCAM):āc.558T>Cā(p.Tyr186=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
EPCAM
NM_002354.3 splice_region, synonymous
NM_002354.3 splice_region, synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.68
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 -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
Variant 2-47378955-T-C is Benign according to our data. Variant chr2-47378955-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 239133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=2.68 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPCAM | NM_002354.3 | c.558T>C | p.Tyr186= | splice_region_variant, synonymous_variant | 6/9 | ENST00000263735.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPCAM | ENST00000263735.9 | c.558T>C | p.Tyr186= | splice_region_variant, synonymous_variant | 6/9 | 1 | NM_002354.3 | P1 | |
EPCAM | ENST00000405271.5 | c.642T>C | p.Tyr214= | splice_region_variant, synonymous_variant | 7/10 | 5 | |||
EPCAM | ENST00000490733.1 | n.407T>C | splice_region_variant, non_coding_transcript_exon_variant | 4/6 | 3 | ||||
EPCAM | ENST00000456133.5 | c.642T>C | p.Tyr214= | splice_region_variant, synonymous_variant, NMD_transcript_variant | 7/11 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1284330Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0AN XY: 649040
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
1284330
Hom.:
Cov.:
20
AF XY:
AC XY:
0
AN XY:
649040
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary nonpolyposis colorectal neoplasms Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 30, 2016 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 02, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
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