16-68737332-G-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004360.5(CDH1):c.-84G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000707 in 1,174,648 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0033 ( 7 hom., cov: 33)
Exomes 𝑓: 0.00032 ( 6 hom. )
Consequence
CDH1
NM_004360.5 5_prime_UTR
NM_004360.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0350
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 Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 16-68737332-G-A is Benign according to our data. Variant chr16-68737332-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 492675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00333 (508/152342) while in subpopulation AFR AF= 0.0117 (485/41588). AF 95% confidence interval is 0.0108. There are 7 homozygotes in gnomad4. There are 237 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 508 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.-84G>A | 5_prime_UTR_variant | 1/16 | ENST00000261769.10 | NP_004351.1 | ||
CDH1 | NM_001317184.2 | c.-84G>A | 5_prime_UTR_variant | 1/15 | NP_001304113.1 | |||
CDH1 | NM_001317185.2 | c.-1699G>A | 5_prime_UTR_variant | 1/16 | NP_001304114.1 | |||
CDH1 | NM_001317186.2 | c.-1903G>A | 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.-84G>A | 5_prime_UTR_variant | 1/16 | 1 | NM_004360.5 | ENSP00000261769 | P1 | ||
CDH1 | ENST00000566612.5 | c.-84G>A | 5_prime_UTR_variant, NMD_transcript_variant | 1/15 | 1 | ENSP00000454782 | ||||
CDH1 | ENST00000422392.6 | upstream_gene_variant | 1 | ENSP00000414946 | ||||||
CDH1 | ENST00000566510.5 | upstream_gene_variant | 5 | ENSP00000458139 |
Frequencies
GnomAD3 genomes AF: 0.00333 AC: 507AN: 152228Hom.: 7 Cov.: 33
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GnomAD4 exome AF: 0.000316 AC: 323AN: 1022306Hom.: 6 Cov.: 13 AF XY: 0.000279 AC XY: 144AN XY: 516370
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GnomAD4 genome AF: 0.00333 AC: 508AN: 152342Hom.: 7 Cov.: 33 AF XY: 0.00318 AC XY: 237AN XY: 74498
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 25, 2018 | - - |
Malignant tumor of prostate Benign:1
Likely benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at