rs377715562
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001379500.1(COL18A1):c.3250-15G>A 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 0.00199 in 1,543,552 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0022 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0020 ( 18 hom. )
Consequence
COL18A1
NM_001379500.1 splice_polypyrimidine_tract, intron
NM_001379500.1 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.789
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]
SLC19A1 (HGNC:10937): (solute carrier family 19 member 1) The membrane protein encoded by this gene is a transporter of folate and is involved in the regulation of intracellular concentrations of folate. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 21-45509341-G-A is Benign according to our data. Variant chr21-45509341-G-A is described in ClinVar as [Benign]. Clinvar id is 261909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-45509341-G-A is described in Lovd as [Likely_benign]. Variant chr21-45509341-G-A is described in Lovd as [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.3250-15G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000651438.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL18A1 | ENST00000651438.1 | c.3250-15G>A | splice_polypyrimidine_tract_variant, intron_variant | NM_001379500.1 |
Frequencies
GnomAD3 genomes ? AF: 0.00223 AC: 339AN: 152122Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.00368 AC: 528AN: 143294Hom.: 5 AF XY: 0.00391 AC XY: 306AN XY: 78348
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GnomAD4 exome AF: 0.00196 AC: 2733AN: 1391312Hom.: 18 Cov.: 32 AF XY: 0.00210 AC XY: 1440AN XY: 686970
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GnomAD4 genome ? AF: 0.00223 AC: 339AN: 152240Hom.: 2 Cov.: 33 AF XY: 0.00220 AC XY: 164AN XY: 74438
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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:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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