16-68737363-G-GCCCGA
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_004360.5(CDH1):c.-45_-41dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000349 in 1,491,050 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
CDH1
NM_004360.5 5_prime_UTR
NM_004360.5 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.623
Genes affected
CDH1 (HGNC:1748): (cadherin 1) This gene encodes a classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid and ovarian cancer. Loss of function of this gene is thought to contribute to cancer progression by increasing proliferation, invasion, and/or metastasis. The ectodomain of this protein mediates bacterial adhesion to mammalian cells and the cytoplasmic domain is required for internalization. This gene is present in a gene cluster with other members of the cadherin family on chromosome 16. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP6
Variant 16-68737363-G-GCCCGA is Benign according to our data. Variant chr16-68737363-G-GCCCGA is described in ClinVar as [Likely_benign]. Clinvar id is 182374.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 36 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.-45_-41dup | 5_prime_UTR_variant | 1/16 | ENST00000261769.10 | NP_004351.1 | ||
CDH1 | NM_001317184.2 | c.-45_-41dup | 5_prime_UTR_variant | 1/15 | NP_001304113.1 | |||
CDH1 | NM_001317185.2 | c.-1660_-1656dup | 5_prime_UTR_variant | 1/16 | NP_001304114.1 | |||
CDH1 | NM_001317186.2 | c.-1864_-1860dup | 5_prime_UTR_variant | 1/15 | NP_001304115.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDH1 | ENST00000261769.10 | c.-45_-41dup | 5_prime_UTR_variant | 1/16 | 1 | NM_004360.5 | ENSP00000261769 | P1 | ||
CDH1 | ENST00000422392.6 | c.-45_-41dup | 5_prime_UTR_variant | 1/15 | 1 | ENSP00000414946 | ||||
CDH1 | ENST00000566612.5 | c.-45_-41dup | 5_prime_UTR_variant, NMD_transcript_variant | 1/15 | 1 | ENSP00000454782 | ||||
CDH1 | ENST00000566510.5 | c.-45_-41dup | 5_prime_UTR_variant, NMD_transcript_variant | 1/15 | 5 | ENSP00000458139 |
Frequencies
GnomAD3 genomes AF: 0.000237 AC: 36AN: 152194Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.0000120 AC: 16AN: 1338744Hom.: 0 Cov.: 24 AF XY: 0.00000906 AC XY: 6AN XY: 662176
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GnomAD4 genome AF: 0.000236 AC: 36AN: 152306Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19AN XY: 74478
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 07, 2017 | 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. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at