rs13338860
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_001378743.1(CYLD):c.2041+50C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,414,310 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: 𝑓 0.0045 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00070 ( 10 hom. )
Consequence
CYLD
NM_001378743.1 intron
NM_001378743.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.236
Genes affected
CYLD (HGNC:2584): (CYLD lysine 63 deubiquitinase) This gene is encodes a cytoplasmic protein with three cytoskeletal-associated protein-glycine-conserved (CAP-GLY) domains that functions as a deubiquitinating enzyme. Mutations in this gene have been associated with cylindromatosis, multiple familial trichoepithelioma, and Brooke-Spiegler syndrome. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00449 (684/152264) while in subpopulation AFR AF= 0.0149 (621/41556). AF 95% confidence interval is 0.014. There are 6 homozygotes in gnomad4. There are 345 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High AC in GnomAd4 at 684 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYLD | NM_001378743.1 | c.2041+50C>A | intron_variant | ENST00000427738.8 | NP_001365672.1 | |||
LOC105371251 | XR_933542.3 | n.457-2807G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYLD | ENST00000427738.8 | c.2041+50C>A | intron_variant | 5 | NM_001378743.1 | ENSP00000392025 | A1 | |||
ENST00000564510.1 | n.457-2807G>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00448 AC: 682AN: 152148Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00146 AC: 364AN: 249006Hom.: 4 AF XY: 0.00116 AC XY: 157AN XY: 135140
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GnomAD4 exome AF: 0.000704 AC: 888AN: 1262046Hom.: 10 Cov.: 18 AF XY: 0.000628 AC XY: 401AN XY: 638150
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GnomAD4 genome AF: 0.00449 AC: 684AN: 152264Hom.: 6 Cov.: 32 AF XY: 0.00463 AC XY: 345AN XY: 74450
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ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
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Name
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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