Variant 21-45422528-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001379500.1(COL18A1):c.106+17055C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 520,730 control chromosomes in the GnomAD database, including 5,299 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 0.16 ( 2454 hom., cov: 33)

Exomes 𝑓: 0.12 ( 2845 hom. )

Consequence

COL18A1
NM_001379500.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.187

Variant links:

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]

COL18A1 links:

COL18A1-AS1 (HGNC:23132): (COL18A1 antisense RNA 1)

COL18A1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
COL18A1	NM_001379500.1 linkuse as main transcript	c.106+17055C>T	intron_variant		ENST00000651438.1	NP_001366429.1
COL18A1-AS1	NR_027498.1 linkuse as main transcript	n.321G>A	non_coding_transcript_exon_variant	2/3
COL18A1-AS1	NR_028082.1 linkuse as main transcript	n.1405G>A	non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COL18A1	ENST00000651438.1 linkuse as main transcript	c.106+17055C>T	intron_variant			NM_001379500.1	ENSP00000498485	P39060-2
COL18A1-AS1	ENST00000397787.5 linkuse as main transcript	n.1405G>A	non_coding_transcript_exon_variant	2/3	1
COL18A1-AS1	ENST00000485206.1 linkuse as main transcript	n.321G>A	non_coding_transcript_exon_variant	2/3	1

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24263

AN:

152118

Hom.:

2454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.281

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.0995

Gnomad OTH

AF:

0.158

GnomAD3 exomes

AF:

0.129

AC:

28582

AN:

221864

Hom.:

2102

AF XY:

0.125

AC XY:

15052

AN XY:

120042

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.227

Gnomad SAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.0984

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.116

AC:

42910

AN:

368494

Hom.:

2845

Cov.:

AF XY:

0.116

AC XY:

24294

AN XY:

209438

show subpopulations

Gnomad4 AFR exome

AF:

0.276

Gnomad4 AMR exome

AF:

0.126

Gnomad4 ASJ exome

AF:

0.122

Gnomad4 EAS exome

AF:

0.219

Gnomad4 SAS exome

AF:

0.122

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.0954

Gnomad4 OTH exome

AF:

0.128

GnomAD4 genome

AF:

0.160

AC:

24283

AN:

152236

Hom.:

2454

Cov.:

AF XY:

0.161

AC XY:

11982

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.280

Gnomad4 AMR

AF:

0.127

Gnomad4 ASJ

AF:

0.136

Gnomad4 EAS

AF:

0.216

Gnomad4 SAS

AF:

0.122

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.0995

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.121

Hom.:

818

Bravo

AF:

0.165

Asia WGS

AF:

0.168

AC:

586

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.5

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over