chr20-61499482-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001794.5(CDH4):c.170-244081C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000481 in 1,289,150 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000045 ( 0 hom. )
Consequence
CDH4
NM_001794.5 intron
NM_001794.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.119
Genes affected
CDH4 (HGNC:1763): (cadherin 4) This gene is a classical cadherin from the cadherin superfamily. The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Based on studies in chicken and mouse, this cadherin is thought to play an important role during brain segmentation and neuronal outgrowth. In addition, a role in kidney and muscle development is indicated. Of particular interest are studies showing stable cis-heterodimers of cadherins 2 and 4 in cotransfected cell lines. Previously thought to interact in an exclusively homophilic manner, this is the first evidence of cadherin heterodimerization. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 20-61499482-C-T is Benign according to our data. Variant chr20-61499482-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3046991.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH4 | NM_001794.5 | c.170-244081C>T | intron_variant | ENST00000614565.5 | |||
CDH4 | NM_001252338.2 | c.48C>T | p.Cys16= | synonymous_variant | 1/15 | ||
CDH4 | XM_047439812.1 | c.-53-244081C>T | intron_variant | ||||
CDH4 | XM_047439813.1 | c.-53-244081C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH4 | ENST00000614565.5 | c.170-244081C>T | intron_variant | 1 | NM_001794.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152198Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000266 AC: 34AN: 128034Hom.: 0 AF XY: 0.000328 AC XY: 23AN XY: 70106
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GnomAD4 exome AF: 0.0000449 AC: 51AN: 1136834Hom.: 0 Cov.: 30 AF XY: 0.0000574 AC XY: 32AN XY: 557678
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GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152316Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74474
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
CDH4-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 21, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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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