rs2838917

Variant names:

• chr21-45419989-T-C
• rs2838917
• ENST00000397787.5:n.3152A>G

Your query was ambiguous. Multiple possible variants found:

• chr21-45419989-T-C
• chr21-45419989-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000397787.5(COL18A1-AS1):​n.3152A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,050 control chromosomes in the GnomAD database, including 29,837 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 0.62 (29830 hom., cov: 32)
  • Exomes 𝑓: 0.80 (7 hom.)
• Consequence: COL18A1-AS1 ENST00000397787.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313
• Publications: 14 publications found

Genes affected

COL18A1-AS1 (HGNC:23132): (COL18A1 antisense RNA 1)

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 Gene-Disease associations (from GenCC):

• Knobloch syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
• Knobloch syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet
• hereditary glaucoma, primary closed-angle

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL18A1	NM_001379500.1	c.106+14516T>C		intron_variant	Intron 2 of 41	ENST00000651438.1	NP_001366429.1
COL18A1-AS1	NR_027498.1	n.2068A>G		non_coding_transcript_exon_variant	Exon 3 of 3
COL18A1-AS1	NR_028082.1	n.3152A>G		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL18A1-AS1	ENST00000397787.5	n.3152A>G		non_coding_transcript_exon_variant	Exon 3 of 3	1
COL18A1-AS1	ENST00000485206.1	n.2068A>G		non_coding_transcript_exon_variant	Exon 3 of 3	1
COL18A1	ENST00000651438.1	c.106+14516T>C		intron_variant	Intron 2 of 41		NM_001379500.1	ENSP00000498485.1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93778 AN: 151910 Hom.: 29836 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.800 AC: 16 AN: 20 Hom.: 7 Cov.: 0 AF XY: 0.750 AC XY: 12 AN XY: 16

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 9 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.833 AC: 5 AN: 6

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.617 AC: 93801 AN: 152030 Hom.: 29830 Cov.: 32 AF XY: 0.620 AC XY: 46061 AN XY: 74316

African (AFR) AF: 0.461 AC: 19111 AN: 41466

American (AMR) AF: 0.559 AC: 8527 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2456 AN: 3472

East Asian (EAS) AF: 0.541 AC: 2780 AN: 5134

South Asian (SAS) AF: 0.701 AC: 3376 AN: 4818

European-Finnish (FIN) AF: 0.739 AC: 7819 AN: 10586

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47492 AN: 67978

Other (OTH) AF: 0.628 AC: 1326 AN: 2110

Alfa AF: 0.667 Hom.: 135089

Bravo AF: 0.594

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.28
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2838917; hg19: chr21-46839904; COSMIC: COSV67268477;