rs62216320

Positions:

• chr21-45453154-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001379500.1(COL18A1):​c.107-15088T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 150,196 control chromosomes in the GnomAD database, including 1,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1449 hom., cov: 34)
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.904

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 21-45453154-T-C is Benign according to our data. Variant chr21-45453154-T-C is described in ClinVar as [Benign]. Clinvar id is 1231975.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL18A1	NM_001379500.1	c.107-15088T>C		intron_variant		ENST00000651438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL18A1	ENST00000651438.1	c.107-15088T>C		intron_variant			NM_001379500.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19533 AN: 150082 Hom.: 1449 Cov.: 34

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.0911

Gnomad OTH AF: 0.124

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.130 AC: 19550 AN: 150196 Hom.: 1449 Cov.: 34 AF XY: 0.132 AC XY: 9703 AN XY: 73472

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.0911

Gnomad4 OTH AF: 0.124

Alfa AF: 0.108 Hom.: 136

Bravo AF: 0.131

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

Feb 23, 2021

This variant is associated with the following publications: (PMID: 20817676) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs62216320; hg19: chr21-46873068;