21-45405298-C-CCCGGGGGTCCCGGGGGTCGGCTGGGTCCTGCGGGGGTCCTGCGGGGGTCCT

Variant names:

• chr21-45405298-C-CCCGGGGGTCCCGGGGGTCGGCTGGGTCCTGCGGGGGTCCTGCGGGGGTCCT
• rs1461390052
• NM_001379500.1:c.11+57_11+58insCCGGGGGTCCCGGGGGTCGGCTGGGTCCTGCGGGGGTCCTGCGGGGGTCCT

Variant summary

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

The NM_001379500.1(COL18A1):​c.11+57_11+58insCCGGGGGTCCCGGGGGTCGGCTGGGTCCTGCGGGGGTCCTGCGGGGGTCCT 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 0.0024 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00012 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500

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+57_11+58insCCGGGGGTCCCGGGGGTCGGCTGGGTCCTGCGGGGGTCCTGCGGGGGTCCT		intron_variant	Intron 1 of 41	ENST00000651438.1	NP_001366429.1
BNAT1	NR_183526.1	n.197-803_197-802insAGGACCCCCGCAGGACCCCCGCAGGACCCAGCCGACCCCCGGGACCCCCGG		intron_variant	Intron 1 of 1
BNAT1	NR_183527.1	n.181+61_181+62insAGGACCCCCGCAGGACCCCCGCAGGACCCAGCCGACCCCCGGGACCCCCGG		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL18A1	ENST00000651438.1	c.11+57_11+58insCCGGGGGTCCCGGGGGTCGGCTGGGTCCTGCGGGGGTCCTGCGGGGGTCCT		intron_variant	Intron 1 of 41		NM_001379500.1	ENSP00000498485.1

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 120 AN: 49902 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000535

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: 0.000155

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000125 AC: 59 AN: 472012 Hom.: 1 Cov.: 5 AF XY: 0.000118 AC XY: 27 AN XY: 228530

Gnomad4 AFR exome AF: 0.00159

Gnomad4 AMR exome AF: 0.000453

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000162

Gnomad4 SAS exome AF: 0.000219

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000918

Gnomad4 OTH exome AF: 0.0000503

GnomAD4 genome AF: 0.00240 AC: 120 AN: 49936 Hom.: 0 Cov.: 0 AF XY: 0.00184 AC XY: 45 AN XY: 24502

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.000535

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000155

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

LitVar

Other links and lift over

dbSNP: rs1461390052; hg19: chr21-46825213;