chr20-61254865-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001794.5(CDH4):c.97G>A(p.Ala33Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,612,986 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0072 ( 8 hom., cov: 33)
Exomes 𝑓: 0.00074 ( 12 hom. )
Consequence
CDH4
NM_001794.5 missense
NM_001794.5 missense
Scores
1
14
Clinical Significance
Conservation
PhyloP100: 2.17
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008261234).
BP6
?
Variant 20-61254865-G-A is Benign according to our data. Variant chr20-61254865-G-A is described in ClinVar as [Benign]. Clinvar id is 769098.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00724 (1103/152308) while in subpopulation AFR AF= 0.0251 (1041/41550). AF 95% confidence interval is 0.0238. There are 8 homozygotes in gnomad4. There are 535 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1101 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH4 | NM_001794.5 | c.97G>A | p.Ala33Thr | missense_variant | 2/16 | ENST00000614565.5 | |
CDH4 | XM_047439812.1 | c.-126G>A | 5_prime_UTR_variant | 2/16 | |||
CDH4 | XM_047439813.1 | c.-126G>A | 5_prime_UTR_variant | 2/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH4 | ENST00000614565.5 | c.97G>A | p.Ala33Thr | missense_variant | 2/16 | 1 | NM_001794.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00723 AC: 1101AN: 152188Hom.: 8 Cov.: 33
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GnomAD3 exomes AF: 0.00187 AC: 470AN: 251464Hom.: 3 AF XY: 0.00145 AC XY: 197AN XY: 135912
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GnomAD4 exome AF: 0.000744 AC: 1087AN: 1460678Hom.: 12 Cov.: 30 AF XY: 0.000623 AC XY: 453AN XY: 726770
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GnomAD4 genome ? AF: 0.00724 AC: 1103AN: 152308Hom.: 8 Cov.: 33 AF XY: 0.00718 AC XY: 535AN XY: 74466
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
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