chr21-45405298-C-CCT

Position:

• chr21-45405298-C-CCT

Variant summary

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

The NM_001379500.1(COL18A1):​c.11+57_11+58insCT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (485 hom., cov: 0)
  • Exomes 𝑓: 0.085 (2415 hom.)
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 21-45405298-C-CCT is Benign according to our data. Variant chr21-45405298-C-CCT is described in ClinVar as [Benign]. Clinvar id is 1289798.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL18A1	NM_001379500.1	c.11+57_11+58insCT		intron_variant		ENST00000651438.1
BNAT1	NR_183526.1	n.197-803_197-802insAG		intron_variant, non_coding_transcript_variant
BNAT1	NR_183527.1	n.181+61_181+62insAG		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL18A1	ENST00000651438.1	c.11+57_11+58insCT		intron_variant			NM_001379500.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 9813 AN: 49892 Hom.: 482 Cov.: 0

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.00111

Gnomad SAS AF: 0.0830

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.0897

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.0850 AC: 39979 AN: 470588 Hom.: 2415 Cov.: 5 AF XY: 0.0854 AC XY: 19447 AN XY: 227832

Gnomad4 AFR exome AF: 0.0235

Gnomad4 AMR exome AF: 0.0635

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.000487

Gnomad4 SAS exome AF: 0.0279

Gnomad4 FIN exome AF: 0.128

Gnomad4 NFE exome AF: 0.0894

Gnomad4 OTH exome AF: 0.0745

GnomAD4 genome AF: 0.197 AC: 9826 AN: 49926 Hom.: 485 Cov.: 0 AF XY: 0.193 AC XY: 4728 AN XY: 24486

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.00111

Gnomad4 SAS AF: 0.0832

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.198

Alfa AF: 0.0680 Hom.: 12

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: rs1461390052; hg19: chr21-46825213;