rs776751637
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM4BP6_Moderate
The NM_001379500.1(COL18A1):c.2961_2969dup(p.Gly994_Pro996dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.0000038 in 1,580,680 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P986P) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
COL18A1
NM_001379500.1 inframe_insertion
NM_001379500.1 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.76
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 Uncertain_significance. Variant got 0 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_001379500.1.
BP6
Variant 21-45505223-T-TCCCGGCCCC is Benign according to our data. Variant chr21-45505223-T-TCCCGGCCCC is described in ClinVar as [Benign]. Clinvar id is 402552.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL18A1 | NM_001379500.1 | c.2961_2969dup | p.Gly994_Pro996dup | inframe_insertion | 35/42 | ENST00000651438.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL18A1 | ENST00000651438.1 | c.2961_2969dup | p.Gly994_Pro996dup | inframe_insertion | 35/42 | NM_001379500.1 |
Frequencies
GnomAD3 genomes AF: 0.0000135 AC: 2AN: 148324Hom.: 0 Cov.: 34
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GnomAD4 exome AF: 0.00000279 AC: 4AN: 1432356Hom.: 0 Cov.: 32 AF XY: 0.00000421 AC XY: 3AN XY: 712750
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GnomAD4 genome AF: 0.0000135 AC: 2AN: 148324Hom.: 0 Cov.: 34 AF XY: 0.0000138 AC XY: 1AN XY: 72462
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 11% (631/5822) of African chromosomes in ExAC - |
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at