rs9983675

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001379500.1(COL18A1):​c.107-15272A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 151,738 control chromosomes in the GnomAD database, including 3,417 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 3417 hom., cov: 35)

Consequence

COL18A1
NM_001379500.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.390
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL18A1NM_001379500.1 linkuse as main transcriptc.107-15272A>G intron_variant ENST00000651438.1 NP_001366429.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL18A1ENST00000651438.1 linkuse as main transcriptc.107-15272A>G intron_variant NM_001379500.1 ENSP00000498485.1 P39060-2

Frequencies

GnomAD3 genomes
AF:
0.213
AC:
32361
AN:
151620
Hom.:
3417
Cov.:
35
show subpopulations
Gnomad AFR
AF:
0.214
Gnomad AMI
AF:
0.0954
Gnomad AMR
AF:
0.227
Gnomad ASJ
AF:
0.259
Gnomad EAS
AF:
0.248
Gnomad SAS
AF:
0.234
Gnomad FIN
AF:
0.181
Gnomad MID
AF:
0.202
Gnomad NFE
AF:
0.210
Gnomad OTH
AF:
0.230
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.213
AC:
32360
AN:
151738
Hom.:
3417
Cov.:
35
AF XY:
0.214
AC XY:
15847
AN XY:
74162
show subpopulations
Gnomad4 AFR
AF:
0.214
Gnomad4 AMR
AF:
0.226
Gnomad4 ASJ
AF:
0.259
Gnomad4 EAS
AF:
0.248
Gnomad4 SAS
AF:
0.233
Gnomad4 FIN
AF:
0.181
Gnomad4 NFE
AF:
0.210
Gnomad4 OTH
AF:
0.230
Alfa
AF:
0.214
Hom.:
315
Bravo
AF:
0.218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.22
DANN
Benign
0.48
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9

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: rs9983675; hg19: chr21-46872884; API