chr21-45421052-A-ACCCCC

Variant names:

• chr21-45421052-A-ACCCCC
• rs71334065
• NM_001379500.1:c.106+15580_106+15584dupCCCCC

Variant summary

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

The NM_001379500.1(COL18A1):​c.106+15580_106+15584dupCCCCC 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 0.00028 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000060 (0 hom.)
  • 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+15580_106+15584dupCCCCC		intron_variant	Intron 2 of 41	ENST00000651438.1	NP_001366429.1
COL18A1-AS1	NR_027498.1	n.1000_1004dupGGGGG		non_coding_transcript_exon_variant	Exon 3 of 3
COL18A1-AS1	NR_028082.1	n.2084_2088dupGGGGG		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+15580_106+15584dupCCCCC		intron_variant	Intron 2 of 41		NM_001379500.1	ENSP00000498485.1
COL18A1-AS1	ENST00000397787.5	n.2084_2088dupGGGGG		non_coding_transcript_exon_variant	Exon 3 of 3	1
COL18A1-AS1	ENST00000485206.1	n.1000_1004dupGGGGG		non_coding_transcript_exon_variant	Exon 3 of 3	1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 42 AN: 150662 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.000196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000264

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000385

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000355

Gnomad OTH AF: 0.000482

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000600 AC: 3 AN: 50034 Hom.: 0 Cov.: 0 AF XY: 0.0000744 AC XY: 2 AN XY: 26886

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000833

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000820

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000279 AC: 42 AN: 150768 Hom.: 0 Cov.: 33 AF XY: 0.000245 AC XY: 18 AN XY: 73578

Gnomad4 AFR AF: 0.000195

Gnomad4 AMR AF: 0.000264

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000385

Gnomad4 NFE AF: 0.000355

Gnomad4 OTH AF: 0.000477

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

LitVar

Other links and lift over

dbSNP: rs71334065; hg19: chr21-46840967;