Genetic Information
Gene & Transcript Details
Gene
NRAS
Transcript
NM_002524.4
MANE Select
Total Exons
—
Reference Sequence
NC_000001.10
Alternative Transcripts
| ID | Status | Details |
|---|---|---|
| NM_002524.4 | Alternative | 4454 nt | 255–824 |
| NM_002524.5 | MANE Select | 4326 nt | 132–701 |
| NM_002524.3 | Alternative | 4461 nt | 255–824 |
| NM_002524.2 | Alternative | 1963 nt | 254–823 |
Variant Details
HGVS Notation
NM_002524.4:c.159G>A
Protein Change
L53=
Location
Exon 3
(Exon 3 of )
3
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—
Clinical & Population Data
Population Frequency
gnomAD Global Frequency
0.00886 in 100,000
Extremely Rare
ACMG Criteria Applied
PM2
This variant is absent or extremely rare in population databases (PM2 criteria applies).
ClinVar
OpenClassification
Likely Benign
2 publications
Clinical Statement
"This variant has been reported in ClinVar as Likely benign (3 clinical laboratories) and as Benign (3 clinical laboratories) and as Benign by ClinGen RASopathy Variant Curation Expert Panel expert panel."
COSMIC Somatic Evidence
OpenCOSMIC ID
Recurrence
0 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
Accessing full COSMIC database details requires institutional login or subscription.
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 NRAS.
Functional Summary
Error in OpenAI Consolidation. OncoKB: NRASL53=NRASL53=SomaticNCBI Gene:4893|Show additional gene information Variant OverviewNRAS, a GTPase, is mutated in a diverse range of cancers, most frequently in melanoma and thyroid cancer.This is a synonymous mutation and is not annotated by OncoKB. JAX-CKB: No results found
Database Previews
OncoKB
JAX-CKB
Click on previews to view full database entries. External databases may require institutional access.
Computational Analysis
Pathogenicity Predictions
SpliceAIPredictor 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) | 0.04 | 36 bp |
| Donor Loss (DL) | 0.01 | -131 bp |
| Acceptor Gain (AG) | 0.02 | -2 bp |
| Donor Gain (DG) | 0.0 | 254 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)
BP6
BP6 (Unknown (Pre-LLM))
From pre-LLM assessment (LLM Failed)