21-45405285-C-CGGCTGCGGGGGCTGCGG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001379500.1(COL18A1):c.11+55_11+56insCTGCGGGGCTGCGGGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (582 hom., cov: 0)
  • Exomes 𝑓: 0.096 (1132 hom.)
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 21-45405285-C-CGGCTGCGGGGGCTGCGG is Benign according to our data. Variant chr21-45405285-C-CGGCTGCGGGGGCTGCGG is described in ClinVar as [Benign]. Clinvar id is 1231149.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL18A1	NM_001379500.1	c.11+55_11+56insCTGCGGGGCTGCGGGGG		intron_variant		ENST00000651438.1
BNAT1	NR_183526.1	n.197-790_197-789insCCGCAGCCCCCGCAGCC		intron_variant, non_coding_transcript_variant
BNAT1	NR_183527.1	n.181+74_181+75insCCGCAGCCCCCGCAGCC		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL18A1	ENST00000651438.1	c.11+55_11+56insCTGCGGGGCTGCGGGGG		intron_variant			NM_001379500.1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 9088 AN: 78904 Hom.: 579 Cov.: 0

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.00182

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0432

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.112

GnomAD3 exomes AF: 0.0152 AC: 1 AN: 66 Hom.: 0 AF XY: 0.0263 AC XY: 1 AN XY: 38

Gnomad SAS exome AF: 0.00

Gnomad NFE exome AF: 0.0167

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0963 AC: 19633 AN: 203832 Hom.: 1132 Cov.: 3 AF XY: 0.0973 AC XY: 9962 AN XY: 102378

Gnomad4 AFR exome AF: 0.0360

Gnomad4 AMR exome AF: 0.0829

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.000767

Gnomad4 SAS exome AF: 0.0328

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.0885

GnomAD4 genome AF: 0.115 AC: 9100 AN: 78928 Hom.: 582 Cov.: 0 AF XY: 0.115 AC XY: 4366 AN XY: 37996

Gnomad4 AFR AF: 0.0549

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.00183

Gnomad4 SAS AF: 0.0474

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.110

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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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: rs1555966492; hg19: chr21-46825200;