Genetic Information

Gene & Transcript Details

Gene
BRAF
Transcript
NM_001354609.1 MANE Select
Total Exons
—
Reference Sequence
NC_000007.13
Alternative Transcripts
IDStatusDetails
NM_001354609.2 Alternative 9687 nt | 227–2530
NM_001354609.1 Alternative 9702 nt | 226–2529

Variant Details

HGVS Notation
NM_001354609.1:c.1383A>G
Protein Change
Q461=
Location
Exon 11 (Exon 11 of )
11
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.123 in 100,000
Extremely Rare
ACMG Criteria Applied None

ClinVar

Open
Classification
Likely Benign
2 publications
Publications List
PMID: 17344846

Gln461Gln in exon 11 of BRAF: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located near a splice junction. In addition, this variant has been reported to have a freque ncy of 1.5% in the general population (Greenman 2007, Velangi 2004, Davies 2002, rs56216404).

Clinical Statement

"This variant has been reported in ClinVar as Benign (10 clinical laboratories) and as Likely benign (2 clinical laboratories) and as Benign by ClinGen RASopathy Variant Curation Expert Panel expert panel."

COSMIC Somatic Evidence

Open
COSMIC ID
COSM9494963
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 BRAF.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: BRAFQ461=BRAFQ461=SomaticNCBI Gene:673|Show additional gene information Variant OverviewBRAF, an intracellular kinase, is frequently mutated in melanoma, thyroid and lung cancers among others.This is a synonymous mutation and is not annotated by OncoKB. 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 14 bp
- Donor Loss (DL) 0.0 -49 bp
+ Acceptor Gain (AG) 0.01 54 bp
+ Donor Gain (DG) 0.0 146 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:
BP4

BP4 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

BP6

BP6 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)