chr16-50749824-G-A
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_001378743.1(CYLD):c.126G>A(p.Pro42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000359 in 1,614,090 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 Benign (★).
Frequency
Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00036 ( 0 hom. )
Consequence
CYLD
NM_001378743.1 synonymous
NM_001378743.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.620
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 -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 16-50749824-G-A is Benign according to our data. Variant chr16-50749824-G-A is described in ClinVar as [Benign]. Clinvar id is 319498.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.62 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000361 (55/152262) while in subpopulation AMR AF= 0.000392 (6/15290). AF 95% confidence interval is 0.00023. There are 0 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 55 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYLD | NM_001378743.1 | c.126G>A | p.Pro42= | synonymous_variant | 3/19 | ENST00000427738.8 | NP_001365672.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYLD | ENST00000427738.8 | c.126G>A | p.Pro42= | synonymous_variant | 3/19 | 5 | NM_001378743.1 | ENSP00000392025 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000362 AC: 55AN: 152144Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000213 AC: 53AN: 249306Hom.: 0 AF XY: 0.000185 AC XY: 25AN XY: 135262
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GnomAD4 exome AF: 0.000359 AC: 525AN: 1461828Hom.: 0 Cov.: 32 AF XY: 0.000327 AC XY: 238AN XY: 727212
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GnomAD4 genome AF: 0.000361 AC: 55AN: 152262Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26AN XY: 74460
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial multiple trichoepitheliomata Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Familial cylindromatosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Brooke-Spiegler syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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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