Starting

Initialising…

TP53

Final classification

VUS

TP53 c.74+11C>T · p.?

TP53

The TP53 c.74+11C>T (NP_000537.3:p.?) variant has not been observed in somatic cancers in COSMIC and has not been reported in ClinVar.

Gene

TP53

Transcript

NM_000546.5

HGVS · transcript:coding

NM_000546.5:c.74+11C>T

Consequence

N/A

GRCh38

chr17:7676510 G>A

GRCh37

chr17:7579828 G>A

Basis Tavtigian et.al., 2020 - Bayesian adaptation of Richards et.al., 2015 v2.4.0 point-based framework: PM2 supporting (+1) + BP4 supporting (-1) + BP7 supporting (-1) = -1 points, which maps to VUS. ▾

Tavtigian et.al., 2020 - Bayesian adaptation of Richards et.al., 2015 v2.4.0 point-based framework: PM2 supporting (+1) + BP4 supporting (-1) + BP7 supporting (-1) = -1 points, which maps to VUS.

Classification rationale

PM2 BP4BP7 VUS

TP53 c.74+11C>T

The TP53 c.74+11C>T (NP_000537.3:p.?) variant has not been observed in somatic cancers in COSMIC and has not been reported in ClinVar.¹ This variant is absent from gnomAD v2.1 and gnomAD v4.1, supporting rarity below the TP53 VCEP PM2_Supporting threshold of 0.00003.² SpliceAI predicts no significant splice effect with a maximum delta score of 0.01; for a TP53 intronic variant at +11, this supports BP4_Supporting and BP7_Supporting and does not support PP3 or PVS1.³

PM2 + BP4 + BP7 → VUS

1 clinvar ↗

2 gnomad_v2 ↗gnomad_v4 ↗cspec ↗

3 spliceai ↗cspec ↗vcep_flowchart_for_application_of_pp3_2c_bp4_2c_and_bp7pvs1_variant_assessment

Gene diagram · NM_000546.5 · variants mapped to exon structure

TP53 NM_000546.5

Fetching transcript structure from UCSC…

Applied criteria · 3 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 = 0.01).

SpliceAI ↗

Functional No data

No calibrated functional assay or RNA evidence was identified for this variant.

OncoKB ↗

COSMIC

Somatic evidence

COSMIC

This variant has not previously been reported in somatic cancers (COSMIC).

Hotspots

This variant does not lie in a statistically significant cancer hotspot.

COSMIC ↗

Sources & reference links

7Sources

CSpec VCEP

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

COSMIC