chr21-45405285-C-CGGCTGCGG

Position:

• chr21-45405285-C-CGGCTGCGG

Variant summary

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

The NM_001379500.1(COL18A1):​c.11+47_11+54dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1068 hom., cov: 0)
  • Exomes 𝑓: 0.067 (915 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-CGGCTGCGG is Benign according to our data. Variant chr21-45405285-C-CGGCTGCGG is described in ClinVar as [Benign]. Clinvar id is 1259241.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL18A1	NM_001379500.1	c.11+47_11+54dup		intron_variant		ENST00000651438.1
BNAT1	NR_183526.1	n.197-790_197-789insCCGCAGCC		intron_variant, non_coding_transcript_variant
BNAT1	NR_183527.1	n.181+74_181+75insCCGCAGCC		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL18A1	ENST00000651438.1	c.11+47_11+54dup		intron_variant			NM_001379500.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 10667 AN: 78504 Hom.: 1062 Cov.: 0

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.00940

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0411

Gnomad EAS AF: 0.0994

Gnomad SAS AF: 0.0952

Gnomad FIN AF: 0.0774

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0596

Gnomad OTH AF: 0.127

GnomAD3 exomes AF: 0.0455 AC: 3 AN: 66 Hom.: 1 AF XY: 0.0263 AC XY: 1 AN XY: 38

Gnomad SAS exome AF: 0.00

Gnomad NFE exome AF: 0.0500

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0667 AC: 13559 AN: 203386 Hom.: 915 Cov.: 3 AF XY: 0.0659 AC XY: 6736 AN XY: 102186

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.0816

Gnomad4 ASJ exome AF: 0.0468

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.0878

Gnomad4 FIN exome AF: 0.0614

Gnomad4 NFE exome AF: 0.0558

Gnomad4 OTH exome AF: 0.0816

GnomAD4 genome AF: 0.136 AC: 10676 AN: 78528 Hom.: 1068 Cov.: 0 AF XY: 0.134 AC XY: 5071 AN XY: 37796

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0411

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.0942

Gnomad4 FIN AF: 0.0774

Gnomad4 NFE AF: 0.0596

Gnomad4 OTH AF: 0.125

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: rs767179082; hg19: chr21-46825200;