Variant chr21-45405285-C-CGGCTGCGG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001379500.1(COL18A1):c.11+47_11+54dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1068 hom., cov: 0)

Exomes 𝑓: 0.067 ( 915 hom. )

Consequence

COL18A1
NM_001379500.1 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.677

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 21-45405285-C-CGGCTGCGG is Benign according to our data. Variant chr21-45405285-C-CGGCTGCGG is described in ClinVar as [Benign]. Clinvar id is 1259241.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
COL18A1	NM_001379500.1 linkuse as main transcript	c.11+47_11+54dup	intron_variant	ENST00000651438.1	NP_001366429.1
BNAT1	NR_183526.1 linkuse as main transcript	n.197-790_197-789insCCGCAGCC	intron_variant, non_coding_transcript_variant
BNAT1	NR_183527.1 linkuse as main transcript	n.181+74_181+75insCCGCAGCC	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL18A1	ENST00000651438.1 linkuse as main transcript	c.11+47_11+54dup		intron_variant			NM_001379500.1	ENSP00000498485		P39060-2

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

10667

AN:

78504

Hom.:

1062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.363

Gnomad AMI

AF:

0.00940

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.0411

Gnomad EAS

AF:

0.0994

Gnomad SAS

AF:

0.0952

Gnomad FIN

AF:

0.0774

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0596

Gnomad OTH

AF:

0.127

GnomAD3 exomes

AF:

0.0455

AC:

AN:

Hom.:

AF XY:

0.0263

AC XY:

AN XY:

show subpopulations

Gnomad SAS exome

AF:

0.00

Gnomad NFE exome

AF:

0.0500

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0667

AC:

13559

AN:

203386

Hom.:

915

Cov.:

AF XY:

0.0659

AC XY:

6736

AN XY:

102186

show subpopulations

Gnomad4 AFR exome

AF:

0.378

Gnomad4 AMR exome

AF:

0.0816

Gnomad4 ASJ exome

AF:

0.0468

Gnomad4 EAS exome

AF:

0.132

Gnomad4 SAS exome

AF:

0.0878

Gnomad4 FIN exome

AF:

0.0614

Gnomad4 NFE exome

AF:

0.0558

Gnomad4 OTH exome

AF:

0.0816

GnomAD4 genome

AF:

0.136

AC:

10676

AN:

78528

Hom.:

1068

Cov.:

AF XY:

0.134

AC XY:

5071

AN XY:

37796

show subpopulations

Gnomad4 AFR

AF:

0.363

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.0411

Gnomad4 EAS

AF:

0.100

Gnomad4 SAS

AF:

0.0942

Gnomad4 FIN

AF:

0.0774

Gnomad4 NFE

AF:

0.0596

Gnomad4 OTH

AF:

0.125

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

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