Back
LYFE SCIENCES
Project: HERA
NM_000264.5:c.-9_-4del
p.?  ·  PTCH1
ACMG/AMP
Starting
Initialising…
0%
Legacy Engine
Ready
View Legacy →
Classification rationale
1

The PTCH1 NM_000264.5:c.-9_-4del (NP_000255.2:p.?) variant has been reported in ClinVar, where current submissions classify it as benign or likely benign.

clinvar ↗
2

This variant is common in population databases, with an allele frequency of 1.31180% in gnomAD v4.1, 0.75389% in gnomAD v2.1, and 1.26862% in gnomAD-Canada, which is above the non-VCEP BA1 benign threshold of 1%.

gnomad_v4 ↗ gnomad_v2 ↗ gnomad_canada ↗
3

In silico splice prediction does not support a splice-disrupting effect, with SpliceAI showing a maximum delta score of 0.01.

spliceai ↗
Applied criteria
Met
Not met
Not assessed
N/A
Very strong
Strong
Moderate
Supporting
Pathogenic evidence
PVS
PVS1
PS
PS1
PS2
PS3
PS4
PM
PM1
PM2
PM3
PM4
PM5
PM6
PP
PP1
PP2
PP3
PP4
PP5
Benign evidence
BA
BA1
BS
BS1
BS2
BS3
BS4
BP
BP1
BP2
BP3
BP4
BP5
BP6
BP7
PVS1
—
—
Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
  • —
Rule
—
Publications
—
Research and evidence
gnomAD v2.1 evidence
v2.1
gnomAD v4.1 evidence
v4.1
01
Population
gnomAD v2.1This variant is present in gnomAD v2.1 (AF= 0.00753893; MAF= 0.75389%, 214/28386 alleles, homozygotes = 1) and has highest observed frequency in the Remaining individuals population (AF= 0.0125285; MAF= 1.25285%, 11/878 alleles, homozygotes = 1); grpmax FAF= 0.0111152.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 0.013118; MAF= 1.31180%, 15266/1163744 alleles, homozygotes = 127) and has highest observed frequency in the Middle Eastern population (AF= 0.0230931; MAF= 2.30931%, 66/2858 alleles, homozygotes = 2); grpmax FAF= 0.0186244.
gnomAD CanadaThis variant is present in gnomAD-Canada v1.0 (AF= 0.0126862; MAF= 1.26862%, 230/18130 alleles, homozygotes = 0) and has highest observed frequency in the sas population (AF= 0.0155786; grpmax FAF95= 0.0104388).
gnomAD v2 ↗ gnomAD v4 ↗ gnomAD 🇨🇦 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Benign (7 clinical laboratories) and as Likely benign (4 clinical laboratories) and as benign (1 clinical laboratory). (ClinVarID = 193070)
ClinVar ↗
03
Functional
No functional summary recorded.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant has not previously been reported in somatic cancers (COSMIC).
COSMIC ↗
06
Cancer hotspots
No cancer hotspot summary recorded.