rs200143450
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001379500.1(COL18A1):c.2158-9C>T 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 0.00119 in 1,613,404 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00081 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0012 ( 6 hom. )
Consequence
COL18A1
NM_001379500.1 splice_polypyrimidine_tract, intron
NM_001379500.1 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.85
Genes affected
COL18A1 (HGNC:2195): (collagen type XVIII alpha 1 chain) This gene encodes the alpha chain of type XVIII collagen. This collagen is one of the multiplexins, extracellular matrix proteins that contain multiple triple-helix domains (collagenous domains) interrupted by non-collagenous domains. A long isoform of the protein has an N-terminal domain that is homologous to the extracellular part of frizzled receptors. Proteolytic processing at several endogenous cleavage sites in the C-terminal domain results in production of endostatin, a potent antiangiogenic protein that is able to inhibit angiogenesis and tumor growth. Mutations in this gene are associated with Knobloch syndrome. The main features of this syndrome involve retinal abnormalities, so type XVIII collagen may play an important role in retinal structure and in neural tube closure. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
BP6
Variant 21-45492526-C-T is Benign according to our data. Variant chr21-45492526-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 447118.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}. Variant chr21-45492526-C-T is described in Lovd as [Likely_benign].
BS2
High Homozygotes in GnomAd4 at 2 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL18A1 | NM_001379500.1 | c.2158-9C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000651438.1 | |||
COL18A1 | NM_030582.4 | c.2698-9C>T | splice_polypyrimidine_tract_variant, intron_variant | ||||
COL18A1 | NM_130444.3 | c.3403-9C>T | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL18A1 | ENST00000651438.1 | c.2158-9C>T | splice_polypyrimidine_tract_variant, intron_variant | NM_001379500.1 | |||||
COL18A1 | ENST00000355480.10 | c.2698-9C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
COL18A1 | ENST00000342220.9 | c.199-9C>T | splice_polypyrimidine_tract_variant, intron_variant | 2 | |||||
COL18A1 | ENST00000359759.8 | c.3403-9C>T | splice_polypyrimidine_tract_variant, intron_variant | 5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000815 AC: 124AN: 152186Hom.: 2 Cov.: 33
GnomAD3 genomes
AF:
AC:
124
AN:
152186
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000822 AC: 205AN: 249252Hom.: 1 AF XY: 0.000842 AC XY: 114AN XY: 135360
GnomAD3 exomes
AF:
AC:
205
AN:
249252
Hom.:
AF XY:
AC XY:
114
AN XY:
135360
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00123 AC: 1796AN: 1461100Hom.: 6 Cov.: 34 AF XY: 0.00125 AC XY: 910AN XY: 726830
GnomAD4 exome
AF:
AC:
1796
AN:
1461100
Hom.:
Cov.:
34
AF XY:
AC XY:
910
AN XY:
726830
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000814 AC: 124AN: 152304Hom.: 2 Cov.: 33 AF XY: 0.000725 AC XY: 54AN XY: 74472
GnomAD4 genome
AF:
AC:
124
AN:
152304
Hom.:
Cov.:
33
AF XY:
AC XY:
54
AN XY:
74472
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Knobloch syndrome Uncertain:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 01, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at