chr4-108832392-G-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_198721.4(COL25A1):c.1698C>A(p.Pro566=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000944 in 1,610,564 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000058 ( 0 hom. )
Consequence
COL25A1
NM_198721.4 synonymous
NM_198721.4 synonymous
Scores
3
9
Clinical Significance
Conservation
PhyloP100: 0.845
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 -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.017210811).
BP6
?
Variant 4-108832392-G-T is Benign according to our data. Variant chr4-108832392-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 738694.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.845 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000447 (68/152024) while in subpopulation AFR AF= 0.00154 (64/41446). AF 95% confidence interval is 0.00124. There are 0 homozygotes in gnomad4. There are 30 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL25A1 | NM_198721.4 | c.1698C>A | p.Pro566= | synonymous_variant | 32/38 | ENST00000399132.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL25A1 | ENST00000399132.6 | c.1698C>A | p.Pro566= | synonymous_variant | 32/38 | 5 | NM_198721.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000448 AC: 68AN: 151906Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000170 AC: 42AN: 247486Hom.: 0 AF XY: 0.000134 AC XY: 18AN XY: 134312
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GnomAD4 exome AF: 0.0000576 AC: 84AN: 1458540Hom.: 0 Cov.: 28 AF XY: 0.0000413 AC XY: 30AN XY: 725712
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GnomAD4 genome ? AF: 0.000447 AC: 68AN: 152024Hom.: 0 Cov.: 32 AF XY: 0.000404 AC XY: 30AN XY: 74274
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 21, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
Sift4G
Benign
T
Vest4
MVP
ClinPred
T
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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