rs17036526
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_ModerateBA1
The ENST00000405271.5(EPCAM):c.-149+1G>C variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,102 control chromosomes in the GnomAD database, including 5,239 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.24 ( 5239 hom., cov: 31)
Exomes 𝑓: 0.13 ( 0 hom. )
Consequence
EPCAM
ENST00000405271.5 splice_donor
ENST00000405271.5 splice_donor
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.634
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 Likely_benign. Variant got -6 ACMG points.
PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.06316812 fraction of the gene. Cryptic splice site detected, with MaxEntScore 5.5, offset of -25, new splice context is: gggGTgagg. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPCAM | ENST00000405271.5 | c.-149+1G>C | splice_donor_variant | 5 | |||||
EPCAM | ENST00000456133.5 | c.-149+1G>C | splice_donor_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.243 AC: 36882AN: 151890Hom.: 5224 Cov.: 31
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GnomAD4 exome AF: 0.128 AC: 12AN: 94Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 8AN XY: 64
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ClinVar
Not reported inComputational scores
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Name
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at