16-68819273-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_004360.5(CDH1):c.1566-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
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.1566-7C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000261769.10 | |||
CDH1 | NM_001317184.2 | c.1383-7C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
CDH1 | NM_001317185.2 | c.18-7C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
CDH1 | NM_001317186.2 | c.-254-2728C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH1 | ENST00000261769.10 | c.1566-7C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004360.5 | P1 | |||
ENST00000563916.1 | n.264-3614G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251470Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135912
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461870Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18AN XY: 727234
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74348
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Sep 28, 2017 | Variant summary: The CDH1 c.1566-7C>T variant involves the alteration of a non-conserved intronic nucleotide and 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 2/246246 control chromosomes at a frequency of 0.0000081, which does not exceed the estimated maximal expected allele frequency of a pathogenic CDH1 variant (0.0000283). Multiple clinical diagnostic laboratoriesclassified this variant as likely benign without additional information to allow for an independent evaluation. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 06, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Hereditary diffuse gastric adenocarcinoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 19, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at