rs7279445

Variant names:

• chr21-45500004-C-T
• rs7279445
• NM_001379500.1:c.2683+2343C>T

Variant summary

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

The NM_001379500.1(COL18A1):​c.2683+2343C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,878 control chromosomes in the GnomAD database, including 24,727 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 0.56 (24727 hom., cov: 32)
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.626
• Publications: 23 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 = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL18A1	NM_001379500.1	c.2683+2343C>T		intron_variant	Intron 32 of 41	ENST00000651438.1	NP_001366429.1
COL18A1	NM_130444.3	c.3928+2343C>T		intron_variant	Intron 31 of 40		NP_569711.2
COL18A1	NM_030582.4	c.3223+2343C>T		intron_variant	Intron 31 of 40		NP_085059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL18A1	ENST00000651438.1	c.2683+2343C>T		intron_variant	Intron 32 of 41		NM_001379500.1	ENSP00000498485.1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85089 AN: 151760 Hom.: 24706 Cov.: 32

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.561 AC: 85155 AN: 151878 Hom.: 24727 Cov.: 32 AF XY: 0.562 AC XY: 41724 AN XY: 74224

African (AFR) AF: 0.714 AC: 29527 AN: 41382

American (AMR) AF: 0.555 AC: 8469 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1950 AN: 3470

East Asian (EAS) AF: 0.427 AC: 2199 AN: 5148

South Asian (SAS) AF: 0.494 AC: 2380 AN: 4816

European-Finnish (FIN) AF: 0.561 AC: 5918 AN: 10556

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32943 AN: 67940

Other (OTH) AF: 0.551 AC: 1162 AN: 2110

Alfa AF: 0.512 Hom.: 74086

Bravo AF: 0.567

Asia WGS AF: 0.456 AC: 1590 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	1.4
DANN	Benign	0.30
PhyloP100		-0.63
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: rs7279445; hg19: chr21-46919918;