Genetic Information

Gene & Transcript Details

Gene
HRAS
Transcript
NM_176795.4 MANE Select
Total Exons
—
Reference Sequence
NC_000011.9
Alternative Transcripts
IDStatusDetails
NM_176795.5 Alternative 1260 nt | 215–727
NM_176795.3 Alternative 1251 nt | 189–701
NM_176795.4 Alternative 1268 nt | 206–718
NM_176795.2 Alternative 1143 nt | 189–701

Variant Details

HGVS Notation
NM_176795.4:c.277A>G
Protein Change
I93V
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
0.000708 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)
2 publications
Clinical Statement

"This variant has been reported in ClinVar as Likely benign (1 clinical laboratories) and as Uncertain significance (2 clinical laboratories) and as Uncertain Significance by ClinGen RASopathy Variant Curation Expert Panel expert panel."

COSMIC Somatic Evidence

Open
COSMIC ID
COSM9497547
Recurrence
1 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 HRAS.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: HRASI93VHRASI93VSomaticNCBI Gene:3265|Show additional gene information Variant OverviewHRAS, a GTPase, is altered in a diverse range of cancers including head and neck squamous cell carcinoma, thyroid, and bladder cancer.The HRAS I93V 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 -264 bp
- Donor Loss (DL) 0.0 68 bp
+ Acceptor Gain (AG) 0.0 -174 bp
+ Donor Gain (DG) 0.03 -54 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)