21-45405298-C-CCCGGGGGTCCCGGGGGTCGGCTGGGTCCTGCGGGGGTCCT

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001379500.1(COL18A1):​c.11+57_11+58insCCGGGGGTCCCGGGGGTCGGCTGGGTCCTGCGGGGGTCCT 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 0.0049 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0011 (15 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL18A1	NM_001379500.1	c.11+57_11+58insCCGGGGGTCCCGGGGGTCGGCTGGGTCCTGCGGGGGTCCT		intron_variant	Intron 1 of 41	ENST00000651438.1	NP_001366429.1
BNAT1	NR_183526.1	n.197-803_197-802insAGGACCCCCGCAGGACCCAGCCGACCCCCGGGACCCCCGG		intron_variant	Intron 1 of 1
BNAT1	NR_183527.1	n.181+61_181+62insAGGACCCCCGCAGGACCCAGCCGACCCCCGGGACCCCCGG		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+58insCCGGGGGTCCCGGGGGTCGGCTGGGTCCTGCGGGGGTCCT		intron_variant	Intron 1 of 41		NM_001379500.1	ENSP00000498485.1

Frequencies

GnomAD3 genomes AF: 0.00487 AC: 243 AN: 49900 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00416

Gnomad AMI AF: 0.00615

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.00155

Gnomad EAS AF: 0.00942

Gnomad SAS AF: 0.00528

Gnomad FIN AF: 0.00234

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00303

Gnomad OTH AF: 0.00140

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00114 AC: 536 AN: 471744 Hom.: 15 Cov.: 5 AF XY: 0.00116 AC XY: 264 AN XY: 228402

Gnomad4 AFR exome AF: 0.00120

Gnomad4 AMR exome AF: 0.00476

Gnomad4 ASJ exome AF: 0.000279

Gnomad4 EAS exome AF: 0.0106

Gnomad4 SAS exome AF: 0.000767

Gnomad4 FIN exome AF: 0.000778

Gnomad4 NFE exome AF: 0.000806

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.00491 AC: 245 AN: 49934 Hom.: 2 Cov.: 0 AF XY: 0.00526 AC XY: 129 AN XY: 24502

Gnomad4 AFR AF: 0.00438

Gnomad4 AMR AF: 0.0159

Gnomad4 ASJ AF: 0.00155

Gnomad4 EAS AF: 0.00948

Gnomad4 SAS AF: 0.00529

Gnomad4 FIN AF: 0.00234

Gnomad4 NFE AF: 0.00303

Gnomad4 OTH AF: 0.00138

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;