Variant 21-45405308-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001379500.1(COL18A1):c.11+67G>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 Benign (★).

Frequency

Genomes: 𝑓 0.60 ( 10141 hom., cov: 17)

Exomes 𝑓: 0.57 ( 54406 hom. )

Failed GnomAD Quality Control

Consequence

COL18A1
NM_001379500.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.379

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 Likely_benign. Variant got -6 ACMG points.

BP4

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

BP6

Variant 21-45405308-G-C is Benign according to our data. Variant chr21-45405308-G-C is described in ClinVar as [Benign]. Clinvar id is 1268095.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
COL18A1	NM_001379500.1 linkuse as main transcript	c.11+67G>C	intron_variant	ENST00000651438.1
BNAT1	NR_183526.1 linkuse as main transcript	n.197-812C>G	intron_variant, non_coding_transcript_variant
BNAT1	NR_183527.1 linkuse as main transcript	n.181+52C>G	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.11+67G>C		intron_variant			NM_001379500.1		P39060-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

52717

AN:

88214

Hom.:

10139

Cov.:

FAILED QC

Gnomad AFR

AF:

0.630

Gnomad AMI

AF:

0.519

Gnomad AMR

AF:

0.549

Gnomad ASJ

AF:

0.593

Gnomad EAS

AF:

0.465

Gnomad SAS

AF:

0.592

Gnomad FIN

AF:

0.581

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.596

Gnomad OTH

AF:

0.595

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.575

AC:

259848

AN:

451970

Hom.:

54406

Cov.:

AF XY:

0.575

AC XY:

124928

AN XY:

217402

show subpopulations

Gnomad4 AFR exome

AF:

0.616

Gnomad4 AMR exome

AF:

0.486

Gnomad4 ASJ exome

AF:

0.559

Gnomad4 EAS exome

AF:

0.397

Gnomad4 SAS exome

AF:

0.584

Gnomad4 FIN exome

AF:

0.523

Gnomad4 NFE exome

AF:

0.582

Gnomad4 OTH exome

AF:

0.565

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.598

AC:

52739

AN:

88258

Hom.:

10141

Cov.:

AF XY:

0.596

AC XY:

25239

AN XY:

42360

show subpopulations

Gnomad4 AFR

AF:

0.629

Gnomad4 AMR

AF:

0.549

Gnomad4 ASJ

AF:

0.593

Gnomad4 EAS

AF:

0.465

Gnomad4 SAS

AF:

0.591

Gnomad4 FIN

AF:

0.581

Gnomad4 NFE

AF:

0.596

Gnomad4 OTH

AF:

0.597

Alfa

AF:

0.433

Hom.:

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 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

6.1

DANN

Benign

0.12

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