Variant chr21-45511079-C-A 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.3694-32C>A 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 Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.46 ( 12704 hom., cov: 17)

Exomes 𝑓: 0.40 ( 77414 hom. )

Consequence

COL18A1
NM_001379500.1 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.97

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:

SLC19A1 (HGNC:10937): (solute carrier family 19 member 1) The membrane protein encoded by this gene is a transporter of folate and is involved in the regulation of intracellular concentrations of folate. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]

SLC19A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 21-45511079-C-A is Benign according to our data. Variant chr21-45511079-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 261916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL18A1	NM_001379500.1 linkuse as main transcript	c.3694-32C>A		intron_variant		ENST00000651438.1	NP_001366429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL18A1	ENST00000651438.1 linkuse as main transcript	c.3694-32C>A		intron_variant			NM_001379500.1	ENSP00000498485		P39060-2

Frequencies

GnomAD3 genomes

AF:

0.457

AC:

56287

AN:

123296

Hom.:

12701

Cov.:

show subpopulations

Gnomad AFR

AF:

0.510

Gnomad AMI

AF:

0.376

Gnomad AMR

AF:

0.435

Gnomad ASJ

AF:

0.404

Gnomad EAS

AF:

0.560

Gnomad SAS

AF:

0.497

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.493

Gnomad NFE

AF:

0.430

Gnomad OTH

AF:

0.477

GnomAD3 exomes

AF:

0.452

AC:

64912

AN:

143558

Hom.:

14731

AF XY:

0.453

AC XY:

34809

AN XY:

76788

show subpopulations

Gnomad AFR exome

AF:

0.511

Gnomad AMR exome

AF:

0.441

Gnomad ASJ exome

AF:

0.396

Gnomad EAS exome

AF:

0.571

Gnomad SAS exome

AF:

0.488

Gnomad FIN exome

AF:

0.442

Gnomad NFE exome

AF:

0.421

Gnomad OTH exome

AF:

0.466

GnomAD4 exome

AF:

0.399

AC:

360959

AN:

905792

Hom.:

77414

Cov.:

AF XY:

0.404

AC XY:

188013

AN XY:

465722

show subpopulations

Gnomad4 AFR exome

AF:

0.432

Gnomad4 AMR exome

AF:

0.427

Gnomad4 ASJ exome

AF:

0.391

Gnomad4 EAS exome

AF:

0.581

Gnomad4 SAS exome

AF:

0.475

Gnomad4 FIN exome

AF:

0.453

Gnomad4 NFE exome

AF:

0.373

Gnomad4 OTH exome

AF:

0.414

GnomAD4 genome

AF:

0.456

AC:

56295

AN:

123364

Hom.:

12704

Cov.:

AF XY:

0.458

AC XY:

26968

AN XY:

58906

show subpopulations

Gnomad4 AFR

AF:

0.510

Gnomad4 AMR

AF:

0.434

Gnomad4 ASJ

AF:

0.404

Gnomad4 EAS

AF:

0.561

Gnomad4 SAS

AF:

0.497

Gnomad4 FIN

AF:

0.451

Gnomad4 NFE

AF:

0.430

Gnomad4 OTH

AF:

0.472

Alfa

AF:

0.416

Hom.:

2034

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.47

DANN

Benign

0.23

BranchPoint Hunter

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

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