rs2236451
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The ENST00000355480.10(COL18A1):āc.639A>Gā(p.Pro213=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,590,346 control chromosomes in the GnomAD database, including 93,578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.39 ( 12049 hom., cov: 33)
Exomes š: 0.33 ( 81529 hom. )
Consequence
COL18A1
ENST00000355480.10 synonymous
ENST00000355480.10 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.00
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-1.02).
BP6
?
Variant 21-45456169-A-G is Benign according to our data. Variant chr21-45456169-A-G is described in ClinVar as [Benign]. Clinvar id is 261919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-45456169-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-2 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL18A1 | NM_001379500.1 | c.107-12073A>G | intron_variant | ENST00000651438.1 | |||
COL18A1 | NM_130444.3 | c.639A>G | p.Pro213= | synonymous_variant | 1/41 | ||
COL18A1 | NM_030582.4 | c.639A>G | p.Pro213= | synonymous_variant | 1/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL18A1 | ENST00000355480.10 | c.639A>G | p.Pro213= | synonymous_variant | 1/41 | 1 | |||
COL18A1 | ENST00000651438.1 | c.107-12073A>G | intron_variant | NM_001379500.1 | |||||
COL18A1 | ENST00000359759.8 | c.639A>G | p.Pro213= | synonymous_variant | 1/41 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.387 AC: 58677AN: 151814Hom.: 12038 Cov.: 33
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GnomAD3 exomes AF: 0.335 AC: 78967AN: 236058Hom.: 13821 AF XY: 0.334 AC XY: 42762AN XY: 128100
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GnomAD4 exome AF: 0.333 AC: 479607AN: 1438410Hom.: 81529 Cov.: 65 AF XY: 0.332 AC XY: 236777AN XY: 712200
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GnomAD4 genome ? AF: 0.387 AC: 58724AN: 151936Hom.: 12049 Cov.: 33 AF XY: 0.385 AC XY: 28620AN XY: 74246
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Glaucoma, primary closed-angle Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Knobloch syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Computational scores
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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