NM_001904.3:c.47C>T (p.Pro16Leu) is a missense variant in CTNNB1 absent from gnomAD v2.1 and v4.1 population databases (PM2).1 Multiple in silico tools (REVEL 0.153, BayesDel -0.111, SpliceAI max delta 0.01) concordantly predict a neutral effect (BP4).2 No de novo observations, case-control data, functional studies, segregation data, or ClinVar classifications are available for this variant. The variant has been reported once in the somatic COSMIC database (COSV62719848) but has no established somatic or germline clinical significance. With one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4), the net evidence is equivocal. Applying generic ACMG/AMP 2015 combination rules (PMID:25741868), this variant is classified as a Variant of Uncertain Significance (VUS).3
CTNNB1
Final classification
VUS
CTNNB1 c.47C>T · p.Pro16Leu
CTNNB1
NM_001904.3:c.47C>T (p.Pro16Leu) is a missense variant in CTNNB1 absent from gnomAD v2.1 and v4.1 population databases (PM2).
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 benign; combination = 1 supporting + 1 supporting benign, which maps to VUS.
Classification rationale
PM2
BP4
VUS
CTNNB1 c.47C>T
PM2 + BP4
→
VUS
Gene diagram
· NM_001904.3 · variants mapped to exon structure
CTNNB1
NM_001904.3
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
PS
PM
PP
Benign evidence
BA
BS
BP
—
—
—
Rationale
Select a criterion.
Sources
Evidence used
Gaps remaining
Rule
—
Research & evidence
Population frequency
gnomAD v4.1
gnomAD v2.1
Population frequency
“
Absent from gnomAD v4.1.
“
Absent from gnomAD v2.1.
“
Absent from gnomAD-Canada v1.0.
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.153. BayesDel score = -0.111224.
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. CTNNB1 (β-catenin), a transcriptional activator, is recurrently mutated in various cancers including endometrial and hepatocellular cancers.
COSMIC
Cancer hotspots
Somatic evidence
Not in COSMIC / hotspots
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV62719848, n = 1 times).
Hotspots
This variant does not lie in a statistically significant hotspot.
Sources & reference links