16-68737362-G-C
Position:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004360.5(CDH1):c.-54G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 1,484,350 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0030 ( 11 hom. )
Consequence
CDH1
NM_004360.5 5_prime_UTR
NM_004360.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.994
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 16-68737362-G-C is Benign according to our data. Variant chr16-68737362-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 221181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-68737362-G-C is described in Lovd as [Pathogenic]. Variant chr16-68737362-G-C is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00205 (312/152300) while in subpopulation AMR AF= 0.00445 (68/15298). AF 95% confidence interval is 0.0036. There are 0 homozygotes in gnomad4. There are 138 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 312 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.-54G>C | 5_prime_UTR_variant | 1/16 | ENST00000261769.10 | NP_004351.1 | ||
CDH1 | NM_001317184.2 | c.-54G>C | 5_prime_UTR_variant | 1/15 | NP_001304113.1 | |||
CDH1 | NM_001317185.2 | c.-1669G>C | 5_prime_UTR_variant | 1/16 | NP_001304114.1 | |||
CDH1 | NM_001317186.2 | c.-1873G>C | 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.-54G>C | 5_prime_UTR_variant | 1/16 | 1 | NM_004360.5 | ENSP00000261769 | P1 | ||
CDH1 | ENST00000422392.6 | c.-54G>C | 5_prime_UTR_variant | 1/15 | 1 | ENSP00000414946 | ||||
CDH1 | ENST00000566612.5 | c.-54G>C | 5_prime_UTR_variant, NMD_transcript_variant | 1/15 | 1 | ENSP00000454782 | ||||
CDH1 | ENST00000566510.5 | c.-54G>C | 5_prime_UTR_variant, NMD_transcript_variant | 1/15 | 5 | ENSP00000458139 |
Frequencies
GnomAD3 genomes AF: 0.00205 AC: 312AN: 152190Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
312
AN:
152190
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00305 AC: 4061AN: 1332050Hom.: 11 Cov.: 23 AF XY: 0.00296 AC XY: 1950AN XY: 659118
GnomAD4 exome
AF:
AC:
4061
AN:
1332050
Hom.:
Cov.:
23
AF XY:
AC XY:
1950
AN XY:
659118
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00205 AC: 312AN: 152300Hom.: 0 Cov.: 33 AF XY: 0.00185 AC XY: 138AN XY: 74468
GnomAD4 genome
AF:
AC:
312
AN:
152300
Hom.:
Cov.:
33
AF XY:
AC XY:
138
AN XY:
74468
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary diffuse gastric adenocarcinoma Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Likely benign, criteria provided, single submitter | clinical testing | European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto | Aug 01, 2022 | BS1; PM2 (PMID: 30311375) - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 06, 2023 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 06, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | CDH1: BS1 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at