Variant chr21-45405314-C-G 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.12-65C>G 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 0.23 ( 585 hom., cov: 0)

Exomes 𝑓: 0.067 ( 660 hom. )

Consequence

COL18A1
NM_001379500.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.393

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=-0.91).

BP6

Variant 21-45405314-C-G is Benign according to our data. Variant chr21-45405314-C-G is described in ClinVar as [Benign]. Clinvar id is 1253503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
COL18A1	NM_001379500.1 linkuse as main transcript	c.12-65C>G	intron_variant	ENST00000651438.1
BNAT1	NR_183526.1 linkuse as main transcript	n.197-818G>C	intron_variant, non_coding_transcript_variant
BNAT1	NR_183527.1 linkuse as main transcript	n.181+46G>C	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.12-65C>G		intron_variant			NM_001379500.1		P39060-2

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

8718

AN:

37540

Hom.:

580

Cov.:

show subpopulations

Gnomad AFR

AF:

0.456

Gnomad AMI

AF:

0.0507

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.0258

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.0994

Gnomad MID

AF:

0.308

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.250

GnomAD4 exome

AF:

0.0673

AC:

21679

AN:

322198

Hom.:

660

Cov.:

AF XY:

0.0670

AC XY:

10300

AN XY:

153680

show subpopulations

Gnomad4 AFR exome

AF:

0.345

Gnomad4 AMR exome

AF:

0.0724

Gnomad4 ASJ exome

AF:

0.0812

Gnomad4 EAS exome

AF:

0.0637

Gnomad4 SAS exome

AF:

0.119

Gnomad4 FIN exome

AF:

0.0595

Gnomad4 NFE exome

AF:

0.0579

Gnomad4 OTH exome

AF:

0.0857

GnomAD4 genome

AF:

0.232

AC:

8725

AN:

37570

Hom.:

585

Cov.:

AF XY:

0.229

AC XY:

4177

AN XY:

18262

show subpopulations

Gnomad4 AFR

AF:

0.456

Gnomad4 AMR

AF:

0.132

Gnomad4 ASJ

AF:

0.128

Gnomad4 EAS

AF:

0.0259

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.0994

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.244

Alfa

AF:

0.125

Hom.:

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.8

DANN

Benign

0.13

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