Variant rs2236466 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.1399-48C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0761 in 1,613,576 control chromosomes in the GnomAD database, including 6,177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1293 hom., cov: 33)

Exomes 𝑓: 0.073 ( 4884 hom. )

Consequence

COL18A1
NM_001379500.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.00

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:

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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=-0.89).

BP6

Variant 21-45480419-C-G is Benign according to our data. Variant chr21-45480419-C-G is described in ClinVar as [Benign]. Clinvar id is 261891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
COL18A1	NM_001379500.1 linkuse as main transcript	c.1399-48C>G	intron_variant	ENST00000651438.1
COL18A1	NM_030582.4 linkuse as main transcript	c.1939-48C>G	intron_variant
COL18A1	NM_130444.3 linkuse as main transcript	c.2644-48C>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
COL18A1	ENST00000651438.1 linkuse as main transcript	c.1399-48C>G	intron_variant		NM_001379500.1		P39060-2
COL18A1	ENST00000355480.10 linkuse as main transcript	c.1939-48C>G	intron_variant	1			P39060-1
COL18A1	ENST00000359759.8 linkuse as main transcript	c.2644-48C>G	intron_variant	5		P1	P39060-3

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16543

AN:

152068

Hom.:

1291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0757

Gnomad ASJ

AF:

0.0533

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.0184

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0659

Gnomad OTH

AF:

0.0951

GnomAD3 exomes

AF:

0.0785

AC:

19499

AN:

248366

Hom.:

1112

AF XY:

0.0788

AC XY:

10631

AN XY:

134900

show subpopulations

Gnomad AFR exome

AF:

0.224

Gnomad AMR exome

AF:

0.0513

Gnomad ASJ exome

AF:

0.0513

Gnomad EAS exome

AF:

0.0962

Gnomad SAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.0219

Gnomad NFE exome

AF:

0.0651

Gnomad OTH exome

AF:

0.0715

GnomAD4 exome

AF:

0.0727

AC:

106231

AN:

1461390

Hom.:

4884

Cov.:

AF XY:

0.0737

AC XY:

53598

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.232

Gnomad4 AMR exome

AF:

0.0558

Gnomad4 ASJ exome

AF:

0.0507

Gnomad4 EAS exome

AF:

0.140

Gnomad4 SAS exome

AF:

0.122

Gnomad4 FIN exome

AF:

0.0222

Gnomad4 NFE exome

AF:

0.0646

Gnomad4 OTH exome

AF:

0.0835

GnomAD4 genome

AF:

0.109

AC:

16556

AN:

152186

Hom.:

1293

Cov.:

AF XY:

0.106

AC XY:

7851

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.0753

Gnomad4 ASJ

AF:

0.0533

Gnomad4 EAS

AF:

0.102

Gnomad4 SAS

AF:

0.136

Gnomad4 FIN

AF:

0.0184

Gnomad4 NFE

AF:

0.0659

Gnomad4 OTH

AF:

0.0941

Alfa

AF:

0.0409

Hom.:

Bravo

AF:

0.117

Asia WGS

AF:

0.116

AC:

403

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.29

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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