16-68801719-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_004360.5(CDH1):c.213C>T(p.Leu71=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L71L) has been classified as Likely benign.
Frequency
Consequence
NM_004360.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.213C>T | p.Leu71= | synonymous_variant | 3/16 | ENST00000261769.10 | |
CDH1 | NM_001317184.2 | c.213C>T | p.Leu71= | synonymous_variant | 3/15 | ||
CDH1 | NM_001317185.2 | c.-1403C>T | 5_prime_UTR_variant | 3/16 | |||
CDH1 | NM_001317186.2 | c.-1607C>T | 5_prime_UTR_variant | 3/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH1 | ENST00000261769.10 | c.213C>T | p.Leu71= | synonymous_variant | 3/16 | 1 | NM_004360.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251416Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135880
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461870Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727242
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74320
ClinVar
Submissions by phenotype
Hereditary diffuse gastric adenocarcinoma Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de InvestigaĆ§Ć£o e InovaĆ§Ć£o em SaĆŗde, University of Porto | Aug 01, 2022 | Not applicable criteria (PMID: 30311375) - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 28, 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 23, 2022 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 29, 2015 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | May 01, 2018 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jul 27, 2020 | - - |
Malignant tumor of breast Benign:1
Likely benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The CDH1 p.Leu71= variant was not identified in the literature nor was it identified in the Cosmic or Zhejiang University databases. The variant was identified in dbSNP (ID: rs376667778) as "With Likely benign allele" and ClinVar (classified as likely benign by Ambry Genetics, Invitae, and GeneDx). The variant was identified in control databases in 11 of 277092 chromosomes at a frequency of 0.00004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 2 of 24018 chromosomes (freq: 0.00008), Other in 3 of 6466 chromosomes (freq: 0.0005), European in 5 of 126616 chromosomes (freq: 0.00004), Finnish in 1 of 25770 chromosomes (freq: 0.00004); it was not observed in the Latino, Ashkenazi Jewish, East Asian, and South Asian populations. The p.Leu71= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at