chr16-68738289-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS2BP4
This summary comes from the ClinGen Evidence Repository: The c.49-8C>T is an intronic variant in the splice acceptor region of intron 1. This variant has an allele frequency of 0.00001 (2/150178) in gnomAD with a maximum frequency of 0.00003 (2/57282) in the European (Non-Finnish) sub-population. This variant has been reported in at least 12 individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2; SCV000529519.4, SCV000557406.3). This variant is predicted to have no impact on splicing by multiple in silico splice site predictors. HumanSpliceFinder predicts that this variant may create an exonic ESS site, but this effect has not been demonstrated experimentally to our knowledge (BP4). In summary, this variant meets criteria to be classified as likely benign based on ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2, BP4. LINK:https://erepo.genome.network/evrepo/ui/classification/CA16608223/MONDO:0007648/007
Frequency
Consequence
NM_004360.5 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.49-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000261769.10 | |||
CDH1 | NM_001317184.2 | c.49-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
CDH1 | NM_001317185.2 | c.-1567-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
CDH1 | NM_001317186.2 | c.-1771-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH1 | ENST00000261769.10 | c.49-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004360.5 | P1 | |||
CDH1 | ENST00000422392.6 | c.49-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
CDH1 | ENST00000566612.5 | c.49-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 1 | |||||
CDH1 | ENST00000566510.5 | c.49-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000128 AC: 2AN: 156612Hom.: 0 AF XY: 0.0000242 AC XY: 2AN XY: 82622
GnomAD4 exome AF: 0.0000261 AC: 36AN: 1380112Hom.: 0 Cov.: 28 AF XY: 0.0000264 AC XY: 18AN XY: 682008
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Nov 28, 2016 | - - |
Hereditary diffuse gastric adenocarcinoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 03, 2020 | - - |
CDH1-related diffuse gastric and lobular breast cancer syndrome Benign:1
Likely benign, reviewed by expert panel | curation | ClinGen CDH1 Variant Curation Expert Panel | Aug 17, 2023 | The c.49-8C>T is an intronic variant in the splice acceptor region of intron 1. This variant has an allele frequency of 0.00001 (2/150178) in gnomAD with a maximum frequency of 0.00003 (2/57282) in the European (Non-Finnish) sub-population. This variant has been reported in at least 12 individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2; SCV000529519.4, SCV000557406.3). This variant is predicted to have no impact on splicing by multiple in silico splice site predictors. HumanSpliceFinder predicts that this variant may create an exonic ESS site, but this effect has not been demonstrated experimentally to our knowledge (BP4). In summary, this variant meets criteria to be classified as likely benign based on ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2, BP4. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 20, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at