21-45421052-AC-ACCCCCCCCCCCC

Variant names:

• chr21-45421052-A-ACCCCCCCCCCC
• NM_001379500.1:c.106+15584_106+15585insCCCCCCCCCCC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001379500.1(COL18A1):​c.106+15584_106+15585insCCCCCCCCCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.451

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]

COL18A1-AS1 (HGNC:23132): (COL18A1 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL18A1	NM_001379500.1	c.106+15584_106+15585insCCCCCCCCCCC		intron_variant	Intron 2 of 41	ENST00000651438.1	NP_001366429.1
COL18A1-AS1	NR_027498.1	n.1004_1005insGGGGGGGGGGG		non_coding_transcript_exon_variant	Exon 3 of 3
COL18A1-AS1	NR_028082.1	n.2088_2089insGGGGGGGGGGG		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL18A1	ENST00000651438.1	c.106+15584_106+15585insCCCCCCCCCCC		intron_variant	Intron 2 of 41		NM_001379500.1	ENSP00000498485.1
COL18A1-AS1	ENST00000397787.5	n.2088_2089insGGGGGGGGGGG		non_coding_transcript_exon_variant	Exon 3 of 3	1
COL18A1-AS1	ENST00000485206.1	n.1004_1005insGGGGGGGGGGG		non_coding_transcript_exon_variant	Exon 3 of 3	1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 150742 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000663 AC: 1 AN: 150852 Hom.: 0 Cov.: 33 AF XY: 0.0000136 AC XY: 1 AN XY: 73610

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-46840967;