chr21-45405285-C-CGGCTGCGGGGCTGCGG

Variant names:

• chr21-45405285-C-CGGCTGCGGGGCTGCGG
• rs767179082
• NM_001379500.1:c.11+54_11+55insCTGCGGGGCTGCGGGG

Variant summary

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

The NM_001379500.1(COL18A1):​c.11+54_11+55insCTGCGGGGCTGCGGGG 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 0.00053 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677

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]

BNAT1 (HGNC:56666): (breast cancer associated ESR1 regulating natural antisense transcript 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.11+54_11+55insCTGCGGGGCTGCGGGG		intron_variant	Intron 1 of 41	ENST00000651438.1	NP_001366429.1
BNAT1	NR_183526.1	n.197-790_197-789insCCGCAGCCCCGCAGCC		intron_variant	Intron 1 of 1
BNAT1	NR_183527.1	n.181+74_181+75insCCGCAGCCCCGCAGCC		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL18A1	ENST00000651438.1	c.11+44_11+45insGGCTGCGGGGCTGCGG		intron_variant	Intron 1 of 41		NM_001379500.1	ENSP00000498485.1

Frequencies

GnomAD3 genomes AF: 0.000532 AC: 42 AN: 78958 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000778

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000588

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000334

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000522

Gnomad OTH AF: 0.000924

GnomAD4 exome AF: 0.000323 AC: 66 AN: 204498 Hom.: 0 Cov.: 3 AF XY: 0.000312 AC XY: 32 AN XY: 102726

Gnomad4 AFR exome AF: 0.00117

Gnomad4 AMR exome AF: 0.000322

Gnomad4 ASJ exome AF: 0.000192

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000281

Gnomad4 NFE exome AF: 0.000346

Gnomad4 OTH exome AF: 0.000191

GnomAD4 genome AF: 0.000532 AC: 42 AN: 78982 Hom.: 0 Cov.: 0 AF XY: 0.000526 AC XY: 20 AN XY: 38022

Gnomad4 AFR AF: 0.000776

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000334

Gnomad4 NFE AF: 0.000522

Gnomad4 OTH AF: 0.000911

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: rs767179082; hg19: chr21-46825200;