Sequence trekkers with Ri

This graphic can be used to illustrate the effects of a variant that simultaneously creates a cryptic splice site and also weakens the canonical splice site. Please see Sequence trekkers for information about the Trekker.

Consider the variant NM_000518.5(HBB):c.90C>T (p.Gly30=). This variant is listed as Pathogenic in Clinvar (VCV000038682.2), and may create a novel 5’ splicing donor site and a frameshift change. The variant is located at the -3 position of the donor site of exon 1 of the hemoglobin beta (HBB) gene. The variant is related to beta Thalassemia.

VMVT models the donor site as a 9 nucleotide sequence made up of the last three bases of the upstream exon and the first 6 bases of the following intron. The above variant (shown in brackets) affects the very first base of the canonical (wildtype) donor sequence:

[C/T]AG|GTTGGT

The variant creates a novel (cryptic) splice site three bases upstream, shifting the reading frame:

CTG|G[C/T]AGGT

To represent both changes with VMVT, use the following code. The corresponding SVG graphics are shown beneath the Java code.

  1. Canonical donor site
import org.monarchinitiative.vmvt.core;

final String ref = "CAGGTTGGT";
final String alt = "TAGGTTGGT";

VmvtGenerator vmvt = new VmvtGenerator();
String svg = vmvt.getDonorWithRi(ref, alt);
Donor trekker with Ri graphic

Sequence Trekker graphic for NM_000518.5(HBB):c.90C>T.

  1. Canonical donor site
import org.monarchinitiative.vmvt.core;

final String ref2 = "CTGGCAGGT";
final String alt2 = "CTGGTAGGT";
vmvt = new VmvtGenerator();
svg = vmvt.getDonorWithRi(ref2, alt2);
Donor trekker with Ri graphic

Sequence Trekker graphic showing a cryptic splice site created by NM_000518.5(HBB):c.90C>T.