21-45405320-C-CCTGCGG
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1
The NM_001379500.1(COL18A1):c.12-59_12-58insCTGCGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0621 in 384,292 control chromosomes in the GnomAD database, including 648 homozygotes. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.15 ( 233 hom., cov: 39)
Exomes 𝑓: 0.053 ( 415 hom. )
Consequence
COL18A1
NM_001379500.1 intron
NM_001379500.1 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.672
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 -10 ACMG points.
BP6
Variant 21-45405320-C-CCTGCGG is Benign according to our data. Variant chr21-45405320-C-CCTGCGG is described in ClinVar as [Benign]. Clinvar id is 1261044.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL18A1 | NM_001379500.1 | c.12-59_12-58insCTGCGG | intron_variant | ENST00000651438.1 | |||
BNAT1 | NR_183526.1 | n.197-825_197-824insCCGCAG | intron_variant, non_coding_transcript_variant | ||||
BNAT1 | NR_183527.1 | n.181+39_181+40insCCGCAG | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL18A1 | ENST00000651438.1 | c.12-59_12-58insCTGCGG | intron_variant | NM_001379500.1 |
Frequencies
GnomAD3 genomes AF: 0.147 AC: 5728AN: 38846Hom.: 230 Cov.: 39
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GnomAD4 exome AF: 0.0525 AC: 18135AN: 345408Hom.: 415 Cov.: 15 AF XY: 0.0526 AC XY: 8661AN XY: 164714
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GnomAD4 genome AF: 0.147 AC: 5728AN: 38884Hom.: 233 Cov.: 39 AF XY: 0.144 AC XY: 2755AN XY: 19070
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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 | GeneDx | May 11, 2021 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at