rs2236484

Variant names:

• chr21-45511770-G-A
• rs2236484
• NM_001379500.1:c.3810-418G>A

Variant summary

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

The NM_001379500.1(COL18A1):​c.3810-418G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,112 control chromosomes in the GnomAD database, including 16,743 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 0.46 (16743 hom., cov: 33)
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.20
• Publications: 11 publications found

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]

SLC19A1 (HGNC:10937): (solute carrier family 19 member 1) The membrane protein encoded by this gene is a transporter of folate and is involved in the regulation of intracellular concentrations of folate. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL18A1	NM_001379500.1	c.3810-418G>A		intron_variant	Intron 41 of 41	ENST00000651438.1	NP_001366429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL18A1	ENST00000651438.1	c.3810-418G>A		intron_variant	Intron 41 of 41		NM_001379500.1	ENSP00000498485.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70475 AN: 151992 Hom.: 16734 Cov.: 33

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.487

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.464 AC: 70509 AN: 152112 Hom.: 16743 Cov.: 33 AF XY: 0.466 AC XY: 34666 AN XY: 74360

African (AFR) AF: 0.561 AC: 23272 AN: 41506

American (AMR) AF: 0.424 AC: 6484 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1299 AN: 3468

East Asian (EAS) AF: 0.559 AC: 2886 AN: 5162

South Asian (SAS) AF: 0.485 AC: 2335 AN: 4816

European-Finnish (FIN) AF: 0.442 AC: 4677 AN: 10592

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28091 AN: 67966

Other (OTH) AF: 0.483 AC: 1019 AN: 2110

Alfa AF: 0.427 Hom.: 8671

Bravo AF: 0.466

Asia WGS AF: 0.516 AC: 1792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.074
DANN	Benign	0.44
PhyloP100		-7.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2236484; hg19: chr21-46931684;