Variant 21-45405221-TG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001379500.1(COL18A1):c.-6del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0017 ( 1 hom. )

Consequence

COL18A1
NM_001379500.1 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.965

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:

BNAT1 (HGNC:):

BNAT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP6

Variant 21-45405221-TG-T is Benign according to our data. Variant chr21-45405221-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 2652790.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr21-45405221-TG-T is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
COL18A1	NM_001379500.1 linkuse as main transcript	c.-6del	5_prime_UTR_variant	1/42	ENST00000651438.1
BNAT1	NR_183526.1 linkuse as main transcript	n.197-726del	intron_variant, non_coding_transcript_variant
BNAT1	NR_183527.1 linkuse as main transcript	n.181+138del	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL18A1	ENST00000651438.1 linkuse as main transcript	c.-6del		5_prime_UTR_variant	1/42		NM_001379500.1		P39060-2

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

AN:

51900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000872

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000362

Gnomad ASJ

AF:

0.0306

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0116

Gnomad NFE

AF:

0.000674

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00136

AC:

AN:

4428

Hom.:

AF XY:

0.00148

AC XY:

AN XY:

2704

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0108

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00238

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00168

AC:

143

AN:

84934

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

AN XY:

45078

show subpopulations

Gnomad4 AFR exome

AF:

0.00162

Gnomad4 AMR exome

AF:

0.00314

Gnomad4 ASJ exome

AF:

0.0260

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000578

Gnomad4 OTH exome

AF:

0.00300

GnomAD4 genome

AF:

0.00117

AC:

AN:

51964

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

AN XY:

25498

show subpopulations

Gnomad4 AFR

AF:

0.0000869

Gnomad4 AMR

AF:

0.000361

Gnomad4 ASJ

AF:

0.0306

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000674

Gnomad4 OTH

AF:

0.00420

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.000563

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

COL18A1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over