21-45405320-C-CCTGCGG

Variant summary

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

The NM_001379500.1(COL18A1):​c.12-59_12-58insCTGCGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0621 in 384,292 control chromosomes in the GnomAD database, including 648 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 233 hom., cov: 39)
Exomes 𝑓: 0.053 ( 415 hom. )

Consequence

COL18A1
NM_001379500.1 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.672
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant 21-45405320-C-CCTGCGG is Benign according to our data. Variant chr21-45405320-C-CCTGCGG is described in ClinVar as [Benign]. Clinvar id is 1261044.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COL18A1NM_001379500.1 linkuse as main transcriptc.12-59_12-58insCTGCGG intron_variant ENST00000651438.1
BNAT1NR_183526.1 linkuse as main transcriptn.197-825_197-824insCCGCAG intron_variant, non_coding_transcript_variant
BNAT1NR_183527.1 linkuse as main transcriptn.181+39_181+40insCCGCAG intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COL18A1ENST00000651438.1 linkuse as main transcriptc.12-59_12-58insCTGCGG intron_variant NM_001379500.1 P39060-2

Frequencies

GnomAD3 genomes
AF:
0.147
AC:
5728
AN:
38846
Hom.:
230
Cov.:
39
show subpopulations
Gnomad AFR
AF:
0.268
Gnomad AMI
AF:
0.0154
Gnomad AMR
AF:
0.0908
Gnomad ASJ
AF:
0.120
Gnomad EAS
AF:
0.00958
Gnomad SAS
AF:
0.174
Gnomad FIN
AF:
0.0524
Gnomad MID
AF:
0.256
Gnomad NFE
AF:
0.0904
Gnomad OTH
AF:
0.165
GnomAD4 exome
AF:
0.0525
AC:
18135
AN:
345408
Hom.:
415
Cov.:
15
AF XY:
0.0526
AC XY:
8661
AN XY:
164714
show subpopulations
Gnomad4 AFR exome
AF:
0.203
Gnomad4 AMR exome
AF:
0.0479
Gnomad4 ASJ exome
AF:
0.0740
Gnomad4 EAS exome
AF:
0.0424
Gnomad4 SAS exome
AF:
0.0967
Gnomad4 FIN exome
AF:
0.0289
Gnomad4 NFE exome
AF:
0.0478
Gnomad4 OTH exome
AF:
0.0608
GnomAD4 genome
AF:
0.147
AC:
5728
AN:
38884
Hom.:
233
Cov.:
39
AF XY:
0.144
AC XY:
2755
AN XY:
19070
show subpopulations
Gnomad4 AFR
AF:
0.268
Gnomad4 AMR
AF:
0.0904
Gnomad4 ASJ
AF:
0.120
Gnomad4 EAS
AF:
0.00961
Gnomad4 SAS
AF:
0.173
Gnomad4 FIN
AF:
0.0524
Gnomad4 NFE
AF:
0.0903
Gnomad4 OTH
AF:
0.161

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 submitterclinical testingGeneDxMay 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.

Other links and lift over

dbSNP: rs1569270282; hg19: chr21-46825235; API