Genetic Information

Gene & Transcript Details

Gene
NF1
Transcript
NM_000267.3 MANE Select
Total Exons
—
Reference Sequence
NC_000017.10
Alternative Transcripts
IDStatusDetails
NM_000267.1 Alternative 8959 nt | 212–8668
NM_000267.3 Alternative 12381 nt | 384–8840
NM_000267.2 Alternative 12331 nt | 334–8790

Variant Details

HGVS Notation
NM_000267.3:c.2033C>T
Protein Change
P678L
Location
Exon 18 (Exon 18 of )
18
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.0305 in 100,000
Extremely Rare
ACMG Criteria Applied PM2
This variant is absent or extremely rare in population databases (PM2 criteria applies).

ClinVar

Open
Classification
Uncertain Significance (VUS)
3 publications
Publications List
Clinical Statement

"This variant has been reported in ClinVar as Likely benign (7 clinical laboratories) and as Benign (4 clinical laboratories) and as Uncertain significance (1 clinical laboratories)."

COSMIC Somatic Evidence

Open
COSMIC ID
COSM6915852
Recurrence
2 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
COSMIC Preview
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Functional Impact & Domains

Functional Domain

Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain.
Related Variants in This Domain
No evidence of other pathogenic variants at this position in gene NF1.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: NF1P678LNF1P678LSomaticNCBI Gene:4763|Show additional gene information Variant OverviewNF1, a negative regulator of RAS, is inactivated by mutation or deletion in various solid and hematologic malignancies.The NF1 P678L mutation has not specifically been reviewed by the OncoKB team, and therefore its biological significance is unknown. JAX-CKB: No results found

Database Previews
OncoKB
OncoKB Preview
JAX-CKB
JAX-CKB Preview

Click on previews to view full database entries. External databases may require institutional access.

Computational Analysis

Pathogenicity Predictions

SpliceAI
Predictor Consensus
Mixed/VUS
PP3 Applied
No
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.0 113 bp
- Donor Loss (DL) 0.0 224 bp
+ Acceptor Gain (AG) 0.0 -26 bp
+ Donor Gain (DG) 0.0 218 bp
High impact (≥0.5) Medium impact (0.2-0.49) Low impact (<0.2)

VCEP Guidelines

Applied ACMG/AMP Criteria (VCEP Specific)

Filter Criteria:
PM2

PM2 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

BP4

BP4 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)