rs11911327

chr21-45428241-C-Tchr21-45428241-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379500.1(COL18A1):c.106+22768C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0394 in 152,174 control chromosomes in the GnomAD database, including 318 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.039 (318 hom., cov: 33)
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL18A1	NM_001379500.1	c.106+22768C>T		intron_variant		ENST00000651438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL18A1	ENST00000651438.1	c.106+22768C>T		intron_variant			NM_001379500.1

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5976 AN: 152056 Hom.: 314 Cov.: 33

Gnomad AFR AF: 0.0320

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0234

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.0522

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.0349

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

GnomAD4 genome AF: 0.0394 AC: 5993 AN: 152174 Hom.: 318 Cov.: 33 AF XY: 0.0428 AC XY: 3185 AN XY: 74386

Gnomad4 AFR AF: 0.0320

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0234

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.0520

Gnomad4 FIN AF: 0.0342

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.0350

Alfa AF: 0.0368 Hom.: 49

Bravo AF: 0.0454

Asia WGS AF: 0.111 AC: 386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.18
Dann	Benign	0.57
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11911327; hg19: chr21-46848156;