# BRAF p.V600E (rs113488022)

rsID: rs113488022
ID: chr7:g.140453136A>T
Protein: p.V600E
cDNA: c.620T>A
Consequence: missense_variant
COSMIC: COSM476
Significance: Pathogenic
## AlphaGenome Prediction
Expression LFC: -0.059 (Minimal change)
Splice Score: 0.008 (Low splice impact)
Chromatin: 0.005 (Low chromatin impact)
Top Affected Gene (Ensembl ID when available): ENSG00000103200
Note: AlphaGenome reports this field as a gene-level identifier from its model output.
## ClinVar
Conditions (17 reports):
- Astrocytoma, low-grade, somatic (1 report)
- Carcinoma of colon (CRC) (1 report)
- Cardio-facio-cutaneous syndrome (1 report)
- Cardiovascular phenotype (1 report)
- Cerebral arteriovenous malformation (BAVM) (1 report)
- Cystic epithelial invagination containing papillae lined by columnar epithelium (1 report)
- Lymphangioma (1 report)
- Malignant neoplastic disease (1 report)
- Melanoma (1 report)
- Multiple myeloma (MM) (1 report)
- Nephroblastoma (1 report)
- Non-small cell lung carcinoma (NSCLC) (1 report)
- Nongerminomatous germ cell tumor (1 report)
- Papillary thyroid carcinoma (1 report)
- RASopathy (1 report)
- Vascular malformation (1 report)
- not provided (1 report)
- Review: 2 star(s) (criteria provided, multiple submitters, no conflicts)
- Variant ID: 13961
## Conservation
phyloP (100-way vertebrate): 0.945
phyloP (470-way mammalian): 0.896
phastCons (100-way vertebrate): 0.716
phastCons (470-way mammalian): 0.682
## Expanded Predictions
| Tool | Score | Prediction |
|---|---|---|
| REVEL | 0.931 | - |
| AlphaMissense | 0.985 | Pathogenic |
| ClinPred | 0.993 | D |
| MetaRNN | 0.883 | D |
## Population
gnomAD AF: 0.000004
African/African American: 0
  African/African American (female): 0
  African/African American (male): 0
Latino/Admixed American: 0
  Latino/Admixed American (female): 0
  Latino/Admixed American (male): 0
East Asian: 0
  East Asian (Japanese): 0
  East Asian (Korean): 0
Non-Finnish European: 0
  Non-Finnish European (Bulgarian): 0
  Non-Finnish European (Estonian): 0
  Non-Finnish European (Northwestern): 0
  Non-Finnish European (Other): 0
  Non-Finnish European (Southeastern): 0
  Non-Finnish European (Swedish): 0
South Asian: 0.000033
Ashkenazi Jewish: 0
Finnish: 0
Other: 0
ExAC AF: 0.000016
ExAC non-TCGA AF: 0.000019
## COSMIC
- COSMIC ID: COSM476
- Mutation frequency: 2.830
- Tumor site: biliary_tract
- Mutation nucleotide: T>A
## CGI Drug Associations
| Drug | Association | Tumor Type | Evidence |
|---|---|---|---|
| PLX4720 (BRAF inhibitor) | Responsive | Malignant astrocytoma | Pre-clinical |
| BRAF inhibitor + MEK inhibitors | Responsive | Thyroid | Early trials |
| Pan-RAF inhibitors | Responsive | Cutaneous melanoma | Early trials |
| BRAF inhibitors | Responsive | Ovary | Case report |
| EGFR TK inhibitors | Resistant | Lung adenocarcinoma | Case report |
| Trametinib (MEK inhibitor) | Responsive | Cutaneous melanoma | FDA guidelines |
| BRAF inhibitors | Responsive | Glioma | Pre-clinical |
| Vemurafenib + Cobimetinib (BRAF inhibitor + MEK inhibitor) | Responsive | Cutaneous melanoma | FDA guidelines |
| BRAF inhibitor + PI3K pathway inhibitors | Responsive | Cutaneous melanoma | Pre-clinical |
| Cetuximab (EGFR mAb inhibitor) | Resistant | Colorectal adenocarcinoma | Late trials |
## CIViC
### Cached Evidence (MyVariant)
| Evidence | Type | Level | Disease | Therapies |
|---|---|---|---|---|
| EID79 | DIAGNOSTIC | B | Thyroid Cancer | - |
| EID95 | PREDICTIVE | B | Melanoma | Dabrafenib, Trametinib |
| EID104 | PROGNOSTIC | B | Melanoma | - |
| EID106 | PROGNOSTIC | B | Papillary Thyroid Carcinoma | - |
| EID107 | PROGNOSTIC | B | Papillary Thyroid Carcinoma | - |
| EID105 | PROGNOSTIC | B | Papillary Thyroid Carcinoma | - |
| EID463 | PROGNOSTIC | B | Multiple Myeloma | - |
| EID2123 | PREDICTIVE | D | Melanoma | Sorafenib |
| EID2128 | PREDICTIVE | D | Melanoma | Dabrafenib |
| EID86 | PREDICTIVE | D | Melanoma | Trametinib, Mirdametinib |
| EID2124 | PREDICTIVE | D | Melanoma | Mirdametinib |
| EID2125 | PREDICTIVE | D | Melanoma | Mirdametinib |
| EID2127 | PREDICTIVE | D | Melanoma | Dabrafenib |
| EID2133 | PREDICTIVE | D | Melanoma | Dabrafenib |
| EID2129 | PREDICTIVE | D | Melanoma | Selumetinib |
| EID1405 | PREDICTIVE | B | Colorectal Cancer | Vemurafenib |
| EID2131 | PREDICTIVE | D | Melanoma | Trametinib |
| EID2132 | PREDICTIVE | D | Melanoma | Dabrafenib |
| EID103 | PROGNOSTIC | B | Colorectal Cancer | - |
| EID1430 | PREDICTIVE | C | Gastrointestinal Neuroendocrine Tumor | Dabrafenib, Trametinib, Vemurafenib |
### GraphQL Context
- Evidence Items: 109
- Assertions: 3
| Assertion | AMP Level | Disease | Therapies |
|---|---|---|---|
| AID20 | TIER_I_LEVEL_A | Colorectal Cancer | - |
| AID7 | TIER_I_LEVEL_A | Melanoma | Trametinib, Dabrafenib |
| AID10 | TIER_I_LEVEL_A | Melanoma | Vemurafenib, Cobimetinib |
## Predictions
- CADD: 32.0
- PolyPhen: Probably damaging
## cBioPortal
| Cancer Type | Samples | Frequency |
|---|---|---|
| Colon Adenocarcinoma | 97 | 0.171986 |
| Cutaneous Melanoma | 81 | 0.143617 |
| Lung Adenocarcinoma | 79 | 0.140071 |
| Papillary Thyroid Cancer | 62 | 0.109929 |
| Melanoma of Unknown Primary | 24 | 0.042553 |

## GWAS
No GWAS associations found for this variant.
See also:
  biomcp get gene BRAF
  biomcp search drug --target BRAF
  biomcp variant trials chr7:g.140453136A>T
  biomcp variant articles chr7:g.140453136A>T

[ClinVar](https://www.ncbi.nlm.nih.gov/clinvar/variation/13961/) | [dbSNP](https://www.ncbi.nlm.nih.gov/snp/rs113488022) | [COSMIC](https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=COSM476)

