Variant chr21-45405235-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001379500.1(COL18A1):c.5C>A(p.Ala2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 9/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000055 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

COL18A1
NM_001379500.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.205

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:56666): (breast cancer associated ESR1 regulating natural antisense transcript 1)

BNAT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
COL18A1	NM_001379500.1 link	c.5C>A	p.Ala2Glu	missense_variant	Exon 1 of 42	ENST00000651438.1	NP_001366429.1
BNAT1	NR_183526.1 link	n.197-739G>T		intron_variant	Intron 1 of 1
BNAT1	NR_183527.1 link	n.181+125G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL18A1	ENST00000651438.1 link	c.5C>A	p.Ala2Glu	missense_variant	Exon 1 of 42		NM_001379500.1	ENSP00000498485.1		P39060-2

Frequencies

GnomAD3 genomes

AF:

0.0000545

AC:

AN:

36674

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000111

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000133

AC:

AN:

75252

Hom.:

Cov.:

AF XY:

0.0000253

AC XY:

AN XY:

39526

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000195

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000545

AC:

AN:

36674

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

17672

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000111

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.0060

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.31

M_CAP

Pathogenic

0.96

MetaRNN

Uncertain

0.55

MetaSVM

Uncertain

0.098

PROVEAN

Benign

-0.29

REVEL

Uncertain

0.31

Sift

Benign

0.041

Sift4G

Benign

0.37

Polyphen

0.99

Vest4

0.22

MutPred

0.24

Loss of MoRF binding (P = 0.0047);

MVP

0.89

ClinPred

0.24

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over