Variant chr21-45511078-A-C 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.3694-33A>C 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 (★★).

Frequency

Genomes: 𝑓 0.48 ( 12714 hom., cov: 17)

Exomes 𝑓: 0.42 ( 75627 hom. )

Consequence

COL18A1
NM_001379500.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.82

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

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 21-45511078-A-C is Benign according to our data. Variant chr21-45511078-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 261917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 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.3694-33A>C		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.3694-33A>C		intron_variant			NM_001379500.1	ENSP00000498485		P39060-2

Frequencies

GnomAD3 genomes

AF:

0.478

AC:

56155

AN:

117524

Hom.:

12711

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.472

Gnomad ASJ

AF:

0.420

Gnomad EAS

AF:

0.594

Gnomad SAS

AF:

0.536

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.508

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.496

GnomAD3 exomes

AF:

0.452

AC:

64732

AN:

143278

Hom.:

14686

AF XY:

0.453

AC XY:

34724

AN XY:

76670

show subpopulations

Gnomad AFR exome

AF:

0.509

Gnomad AMR exome

AF:

0.441

Gnomad ASJ exome

AF:

0.395

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:

0.465

GnomAD4 exome

AF:

0.420

AC:

353659

AN:

841384

Hom.:

75627

Cov.:

AF XY:

0.425

AC XY:

184547

AN XY:

433862

show subpopulations

Gnomad4 AFR exome

AF:

0.443

Gnomad4 AMR exome

AF:

0.439

Gnomad4 ASJ exome

AF:

0.427

Gnomad4 EAS exome

AF:

0.628

Gnomad4 SAS exome

AF:

0.477

Gnomad4 FIN exome

AF:

0.482

Gnomad4 NFE exome

AF:

0.395

Gnomad4 OTH exome

AF:

0.444

GnomAD4 genome

AF:

0.478

AC:

56163

AN:

117566

Hom.:

12714

Cov.:

AF XY:

0.483

AC XY:

26897

AN XY:

55650

show subpopulations

Gnomad4 AFR

AF:

0.525

Gnomad4 AMR

AF:

0.471

Gnomad4 ASJ

AF:

0.420

Gnomad4 EAS

AF:

0.595

Gnomad4 SAS

AF:

0.535

Gnomad4 FIN

AF:

0.500

Gnomad4 NFE

AF:

0.446

Gnomad4 OTH

AF:

0.493

Alfa

AF:

0.424

Hom.:

2244

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

-0.92

CADD

Benign

0.14

DANN

Benign

0.13

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