Starting

Initialising…

SETBP1

Final classification

VUS

SETBP1 c.1313C>A · p.Ala438Asp

SETBP1

The SETBP1 c.1313C>A (p.Ala438Asp) variant has not been reported in ClinVar, and no variant-specific reviewed functional evidence was identified in OncoKB.

Gene

SETBP1

Transcript

NM_015559.2

HGVS · transcript:coding

NM_015559.2:c.1313C>A

Consequence

N/A

GRCh38

chr18:44950653 C>A

GRCh37

chr18:42530618 C>A

Basis gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BP4 supporting; combination = 1 supporting + 1 supporting benign, which maps to VUS because the evidence is conflicting. ▾

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BP4 supporting; combination = 1 supporting + 1 supporting benign, which maps to VUS because the evidence is conflicting.

Classification rationale

PM2 BP4 VUS

SETBP1 c.1313C>A

The SETBP1 c.1313C>A (p.Ala438Asp) variant has not been reported in ClinVar, and no variant-specific reviewed functional evidence was identified in OncoKB.¹ This variant is absent from gnomAD v2.1 and gnomAD v4.1, so the observed population frequency is 0 and is below the 0.1% threshold used for PM2 support.² Computational evidence does not support a damaging effect: REVEL is 0.054, BayesDel is -0.44775, and SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, supporting BP4 rather than PP3.³

PM2 + BP4 → VUS

1 clinvar ↗oncokb ↗

2 gnomad_v2 ↗gnomad_v4 ↗

3 revelbayesdelspliceai ↗

Gene diagram · NM_015559.2 · variants mapped to exon structure

SETBP1 NM_015559.2

Fetching transcript structure from UCSC…

Applied criteria · 2 met · select any tile

Met

Not met

Not assessed

N/A

Strength very strong supporting

Pathogenic evidence

PVS

Benign evidence

—

Rationale

Select a criterion.

Sources

Evidence used

Gaps remaining

Rule

—

Research & evidence

Population frequency

gnomAD v4.1

gnomAD v2.1

v4.1

Absent from gnomAD v4.1.

v2.1

Absent from gnomAD v2.1.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v2.1

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v4 ↗ gnomAD v2 ↗

ClinVar

This variant is absent from ClinVar.

ClinVar ↗

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.054. BayesDel score = -0.44775.

SpliceAI ↗

Functional Unknown Oncogenic Effect

OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. SETBP1, an epigenetic remodeling protein, is frequently altered by mutation in a range of hematopoietic malignancies.

OncoKB ↗

COSMIC

Cancer hotspots

Somatic evidence Not in COSMIC / hotspots

COSMIC

This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).

Hotspots

This variant does not lie in a statistically significant hotspot.

COSMIC ↗ Hotspots ↗

Sources & reference links

7Sources

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

COSMIC

Cancer hotspots