Variant chr21-45405320-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001379500.1(COL18A1):c.12-59C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.080 ( 87 hom., cov: 0)

Exomes 𝑓: 0.015 ( 98 hom. )

Consequence

COL18A1
NM_001379500.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.26

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 21-45405320-C-T is Benign according to our data. Variant chr21-45405320-C-T is described in ClinVar as [Benign]. Clinvar id is 1277766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
COL18A1	NM_001379500.1 linkuse as main transcript	c.12-59C>T	intron_variant	ENST00000651438.1
BNAT1	NR_183526.1 linkuse as main transcript	n.197-824G>A	intron_variant, non_coding_transcript_variant
BNAT1	NR_183527.1 linkuse as main transcript	n.181+40G>A	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.12-59C>T		intron_variant			NM_001379500.1		P39060-2

Frequencies

GnomAD3 genomes

AF:

0.0796

AC:

3076

AN:

38644

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0379

Gnomad ASJ

AF:

0.00615

Gnomad EAS

AF:

0.0630

Gnomad SAS

AF:

0.0733

Gnomad FIN

AF:

0.0430

Gnomad MID

AF:

0.0513

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.0649

GnomAD4 exome

AF:

0.0151

AC:

5118

AN:

338368

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

2353

AN XY:

161450

show subpopulations

Gnomad4 AFR exome

AF:

0.153

Gnomad4 AMR exome

AF:

0.0261

Gnomad4 ASJ exome

AF:

0.00649

Gnomad4 EAS exome

AF:

0.0396

Gnomad4 SAS exome

AF:

0.0222

Gnomad4 FIN exome

AF:

0.0284

Gnomad4 NFE exome

AF:

0.00994

Gnomad4 OTH exome

AF:

0.0250

GnomAD4 genome

AF:

0.0796

AC:

3081

AN:

38682

Hom.:

Cov.:

AF XY:

0.0773

AC XY:

1468

AN XY:

18980

show subpopulations

Gnomad4 AFR

AF:

0.187

Gnomad4 AMR

AF:

0.0377

Gnomad4 ASJ

AF:

0.00615

Gnomad4 EAS

AF:

0.0626

Gnomad4 SAS

AF:

0.0738

Gnomad4 FIN

AF:

0.0430

Gnomad4 NFE

AF:

0.0122

Gnomad4 OTH

AF:

0.0633

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.5

DANN

Benign

0.68

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