RareResearch.AI
← Back to atlas

c.861+15C>A

SpliceS3BenignCytoplasmic · predicted
Splice variant · splice site near at position 287 · N-terminal cytoplasmic (intrinsically disordered) · WFS1 (Wolframin)

S3 — Minimal predicted splicing impact (SpliceAI ΔS 0.00)

Interactive 3D Structure

Interactive structure
rotate · zoom · variant + 5 Å neighbors
Fullscreen ↗

AlphaFold wild-type wolframin · the variant site near residue 287 (N-terminal cytoplasmic (intrinsically disordered)) is highlighted.

Variant Assessment

Variant type
Splice
Schema
S3
Minimal predicted splicing impact (SpliceAI ΔS 0.00)
Domain
N-terminal cytoplasmic (intrinsically disordered)
Status
—

Therapeutic Implication · S3

SpliceAI predicts little splicing disruption at this donor (5') site (max ΔS 0.00 < 0.2; acceptor-gain 0.00, acceptor-loss 0.00, donor-gain 0.00, donor-loss 0.00). The variant may be tolerated or act through a weak/again-tissue-specific mechanism; wet-lab RNA validation is the arbiter before any therapeutic call.

Clinical Evidence

ClinVar classificationBenign
Review statuscriteria provided, multiple submitters, no conflicts
Associated conditions—
Population frequency (gnomAD v4)Low frequency · AF 0.010%
cDNA changec.861+15C>A
ClinVar variantNM_006005.3(WFS1):c.861+15C>A
ClinVar accessionVCV001663035
Last evaluated2025/10/07 00:00

Observed in the general population.

Classified for2★ documented assertion

ClinVar classifies this variant as Benign, but does not state what it is classified for. ClinVar records no condition for this variant. A classification without a phenotype and an inheritance mode cannot be read as a statement about Wolfram syndrome risk or severity.

  • Phenotype scope is interpretation of submitted records. The computed values on this card (AlphaMissense, DynaMut2 ΔΔG, pLDDT) are measurements of the model, not of a patient.
  • Presentation cannot be generalised from neighbouring variants: one nucleotide over can present very differently. Structural similarity supports a mechanistic hypothesis, never a phenotype claim.

Review status: 2★ multiple submitters, no conflicts. ClinVar "conditions" is the union of all submissions; 0–1★ entries are submitted conditions, not documented phenotypes.

Population frequency
Global (all ancestries)
AF 0.010% · 166 / 1,610,862 alleles
Homozygotes
2
Highest-frequency population
South Asian · AF 0.157%

Highest in South Asian: AF 0.157% (143 of 91,000 alleles), 15.2x the global figure. The global AF describes the general population, not the at-risk group.

2 homozygotes reported in gnomAD v4 (2 South Asian). gnomAD excludes individuals with severe pediatric disease, so homozygotes in this dataset argue against a fully penetrant severe recessive phenotype and belong in the clinical picture. This is interpretive signal, not a classification.

Ancestry groupAllele freq.AC / ANHom.Carrier est.
South Asian0.157%143 / 91,0002~1 in 320
Remaining individuals0.0080%5 / 62,3360~1 in 6230
European (non-Finnish)0.0015%18 / 1,180,0120~1 in 32780

Source: gnomAD r4, retrieved 2026-08-21. Values are allele frequencies. The carrier estimate is derived from the allele frequency (Hardy-Weinberg, ~2·AF) and is an approximation, not a published figure — where a published carrier frequency exists it outranks this column and is cited on the card.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the c.861+15C>A card below and upload it to Wolfram Intelligence to generate therapeutic-strategy proposals matched to this S3 splice variant and its domain context.

Download c.861+15C>A PDF card ↓or markdown ↓

Full Variant Card

c.861+15C_A — WFS1 Molecular Atlas Card

Variant type: Splice site Boundary: donor (5' splice site) · intronic offset +15 Nearest protein position: ~287 (N-terminal cytoplasmic (intrinsically disordered))

Schema category: S3 — Minimal predicted splicing impact (SpliceAI ΔS 0.00)

SpliceAI predicts little splicing disruption at this donor (5') site (max ΔS 0.00 < 0.2; acceptor-gain 0.00, acceptor-loss 0.00, donor-gain 0.00, donor-loss 0.00). The variant may be tolerated or act through a weak/again-tissue-specific mechanism; wet-lab RNA validation is the arbiter before any therapeutic call.

Splice prediction

  • Affected site: donor (5' splice site), extended splice region
  • SpliceAI delta scores (GRCh38 chr4:6295204 C>A):
    • acceptor gain 0.00 · acceptor loss 0.00
    • donor gain 0.00 · donor loss 0.00
  • Predicted outcome: Minimal predicted splicing impact (SpliceAI ΔS 0.00)

Clinical evidence

Inheritance and scope

Benign — phenotype scope not stated in ClinVar

ClinVar classifies this variant as Benign, but does not state what it is classified for. ClinVar records no condition for this variant. A classification without a phenotype and an inheritance mode cannot be read as a statement about Wolfram syndrome risk or severity.

Phenotype scope is interpretation of submitted records. The computed values on this card (AlphaMissense, DynaMut2 ΔΔG, pLDDT) are measurements of the model, not of a patient. Presentation cannot be generalised from neighbouring variants: one nucleotide over can present very differently. Structural similarity supports a mechanistic hypothesis, never a phenotype claim.

  • Classification: Benign
  • Review status: criteria provided, multiple submitters, no conflicts
  • cDNA change: c.861+15C>A
  • ClinVar accession: VCV001663035
  • Last evaluated: 2025/10/07 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (splice pipeline) on 2026-06-08T07:53:18.705348Z. Schema: reference/card_schema_extension.md (S1–S3). WFS1: UniProt O76024, AlphaFold v6.