chr4-108852290-G-C
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_198721.4(COL25A1):c.1345-10C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 1,589,470 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.011 ( 32 hom., cov: 33)
Exomes 𝑓: 0.0012 ( 34 hom. )
Consequence
COL25A1
NM_198721.4 splice_polypyrimidine_tract, intron
NM_198721.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.007376
2
Clinical Significance
Conservation
PhyloP100: 1.09
Genes affected
COL25A1 (HGNC:18603): (collagen type XXV alpha 1 chain) This gene encodes a brain-specific membrane associated collagen. A product of proteolytic processing of the encoded protein, CLAC (collagenous Alzheimer amyloid plaque component), binds to amyloid beta-peptides found in Alzheimer amyloid plaques but CLAC inhibits rather than facilitates amyloid fibril elongation (PMID: 16300410). A study of over-expression of this collagen in mice, however, found changes in pathology and behavior suggesting that the encoded protein may promote amyloid plaque formation (PMID: 19548013). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
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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=-0.34).
BP6
?
Variant 4-108852290-G-C is Benign according to our data. Variant chr4-108852290-G-C is described in ClinVar as [Benign]. Clinvar id is 767967.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1748/152158) while in subpopulation AFR AF= 0.0398 (1654/41532). AF 95% confidence interval is 0.0382. There are 32 homozygotes in gnomad4. There are 790 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 32 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL25A1 | NM_198721.4 | c.1345-10C>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000399132.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL25A1 | ENST00000399132.6 | c.1345-10C>G | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_198721.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0115 AC: 1744AN: 152040Hom.: 32 Cov.: 33
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GnomAD3 exomes AF: 0.00304 AC: 697AN: 228912Hom.: 14 AF XY: 0.00217 AC XY: 271AN XY: 124614
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GnomAD4 exome AF: 0.00116 AC: 1672AN: 1437312Hom.: 34 Cov.: 28 AF XY: 0.00105 AC XY: 750AN XY: 715220
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GnomAD4 genome ? AF: 0.0115 AC: 1748AN: 152158Hom.: 32 Cov.: 33 AF XY: 0.0106 AC XY: 790AN XY: 74390
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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
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at