rs4413407
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_025212.4(CXXC4):c.*118T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.654 in 507,912 control chromosomes in the GnomAD database, including 114,112 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.72 ( 39104 hom., cov: 24)
Exomes 𝑓: 0.63 ( 75008 hom. )
Consequence
CXXC4
NM_025212.4 3_prime_UTR
NM_025212.4 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.76
Genes affected
CXXC4 (HGNC:24593): (CXXC finger protein 4) This gene encodes a CXXC-type zinc finger domain-containing protein that functions as an antagonist of the canonical wingless/integrated signaling pathway. The encoded protein negatively regulates wingless/integrated signaling through interaction with the post synaptic density protein/ Drosophila disc large tumor suppressor/ zonula occludens-1 protein domain of Dishevelled, a scaffolding protein required for the stabilization of the transcriptional co-activator beta-catenin. In addition, the CXXC domain of this protein has been shown to bind unmethylated CpG dinucleotides, localize to promoters and CpG islands, and interact with the catalytic domain of methylcytosine dioxygenase ten-eleven-translocation 2, an iron and alpha-ketoglutarate-dependent dioxygenase that modifies the methylation status of DNA. In humans, a mutation in this gene has been associated with development of malignant renal cell carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CXXC4 | NM_025212.4 | c.*118T>C | 3_prime_UTR_variant | 3/3 | ENST00000394767.3 | ||
CXXC4 | XM_011532284.3 | c.*118T>C | 3_prime_UTR_variant | 4/4 | |||
CXXC4 | NR_132741.2 | n.433T>C | non_coding_transcript_exon_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CXXC4 | ENST00000394767.3 | c.*118T>C | 3_prime_UTR_variant | 3/3 | 5 | NM_025212.4 | P2 | ||
CXXC4 | ENST00000466963.1 | n.440T>C | non_coding_transcript_exon_variant | 3/3 | 1 | ||||
CXXC4 | ENST00000515509.1 | n.334T>C | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.715 AC: 104714AN: 146408Hom.: 39085 Cov.: 24
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GnomAD4 exome AF: 0.629 AC: 227377AN: 361464Hom.: 75008 Cov.: 6 AF XY: 0.632 AC XY: 120673AN XY: 190788
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GnomAD4 genome ? AF: 0.715 AC: 104746AN: 146448Hom.: 39104 Cov.: 24 AF XY: 0.708 AC XY: 50407AN XY: 71162
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at