21-45405320-C-CCTGCGG

Position:

• chr21-45405320-C-CCTGCGG

Variant summary

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

The NM_001379500.1(COL18A1):​c.12-59_12-58insCTGCGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0621 in 384,292 control chromosomes in the GnomAD database, including 648 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (233 hom., cov: 39)
  • Exomes 𝑓: 0.053 (415 hom.)
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.672

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 21-45405320-C-CCTGCGG is Benign according to our data. Variant chr21-45405320-C-CCTGCGG is described in ClinVar as [Benign]. Clinvar id is 1261044.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL18A1	NM_001379500.1	c.12-59_12-58insCTGCGG		intron_variant		ENST00000651438.1	NP_001366429.1
BNAT1	NR_183526.1	n.197-825_197-824insCCGCAG		intron_variant, non_coding_transcript_variant
BNAT1	NR_183527.1	n.181+39_181+40insCCGCAG		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL18A1	ENST00000651438.1	c.12-59_12-58insCTGCGG		intron_variant			NM_001379500.1	ENSP00000498485

Frequencies

GnomAD3 genomes AF: 0.147 AC: 5728 AN: 38846 Hom.: 230 Cov.: 39

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0908

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00958

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.0904

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.0525 AC: 18135 AN: 345408 Hom.: 415 Cov.: 15 AF XY: 0.0526 AC XY: 8661 AN XY: 164714

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.0479

Gnomad4 ASJ exome AF: 0.0740

Gnomad4 EAS exome AF: 0.0424

Gnomad4 SAS exome AF: 0.0967

Gnomad4 FIN exome AF: 0.0289

Gnomad4 NFE exome AF: 0.0478

Gnomad4 OTH exome AF: 0.0608

GnomAD4 genome AF: 0.147 AC: 5728 AN: 38884 Hom.: 233 Cov.: 39 AF XY: 0.144 AC XY: 2755 AN XY: 19070

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.0904

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.00961

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.0524

Gnomad4 NFE AF: 0.0903

Gnomad4 OTH AF: 0.161

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

- -

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: rs1569270282; hg19: chr21-46825235;