Back
LYFE SCIENCES
Project: HERA
NM_000267.3:c.4686A>G
p.Glu1562=  ·  NF1
Starting
Initialising…
0%
Legacy Engine
Processing…
Classification rationale
1

The NF1 c.4686A>G (p.Glu1562=) variant has been reported in ClinVar predominantly as likely benign or benign, with some uncertain significance submissions.

clinvar ↗
2

This variant is present in population databases, including gnomAD v2.1 at an allele frequency of 0.000226663 (64/282358) and gnomAD v4.1 at an allele frequency of 0.000223144, which is below common benign strong thresholds but inconsistent with absence from controls.

gnomad_v2 ↗ gnomad_v4 ↗
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= 0.000226663; MAF= 0.02267%, 64/282358 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000695217; MAF= 0.06952%, 5/7192 alleles, homozygotes = 0); grpmax FAF= 0.00031301.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 0.000223144; MAF= 0.02231%, 360/1613306 alleles, homozygotes = 2) and has highest observed frequency in the Admixed American population (AF= 0.00044979; MAF= 0.04498%, 27/60028 alleles, homozygotes = 1); grpmax FAF= 0.00031689.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Likely benign (7 clinical laboratories) and as Uncertain significance (3 clinical laboratories) and as Benign (2 clinical laboratories).
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Unknown Oncogenic Effect
OncoKB oncogenicity for this specific variant: Unknown Oncogenic Effect (variant has not been individually curated).
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 does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueE1562
Hotspots ↗