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Here you can see the gene and the variant being analyzed.

We summarize a large amount of clinical data on this gene here. Links are added where available to source information.

Prediction information is summarized here, the percentage shows the likelihood that the variant is pathogenic.

Agreement is a measure (out of 5 stars) of how much our predictors agree between each other. When predictors agree, the prediction is more likely to be correct.

Data quality is a measure (out of 5 stars) of how good the underlying data for this prediction is. This is an assessment of the depth of our alignments and the number of structures available, among other factors.

This table shows literature for this exact position and protein, if it is available.

This table shows literature for this position in homologous proteins, if it is available.

This is a description of our prediction.

This plot illustrates the agreement between different classifiers. If the prediction distributions align on one side it indicates increased certainty in the prediction.

This describes the data quality for this position.

Here are the four factors that contributed most to the prediction. Factors that contributed to a benign prediction are colored blue, pathogenic factors are colored red.

This plot shows all the factors for prediction. Factors that contributed to a benign prediction are colored blue, pathogenic factors are colored red.

This plot shows the conservation on this position.

Here the conservation statistics are described.

This is an interactive structure display. Feel free to play with it after the tour!

This is a list of interactions we found for this position.

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Summary

BRCA1 - ENST00000357654

Gene BRCA1 - ENSG00000012048 | ENSP00000350283 | ENST00000357654
Ensembl | RefSeq | UniProt
Location GRCh38 17:43044295-43125370 Ensembl UCSC
Description BRCA1, DNA repair associated

E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. Acts as a transcriptional activator

Condition(s)
  • Breast-ovarian cancer, familial, 1 (BROVCA1)

    A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate.
    Disease susceptibility is associated with variations affecting the gene represented in this entry. Mutations in BRCA1 are thought to be responsible for more than 80% of inherited breast-ovarian cancer. OMIM

    MedGen: C0027672 C1458155 C0677776 C0006142 C2676676 C1140680 C0678222 OrphaNet: 145 180250 227535 213500
  • Breast cancer (BC)

    A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.
    Disease susceptibility is associated with variations affecting the gene represented in this entry. Mutations in BRCA1 are thought to be responsible for 45% of inherited breast cancer. Moreover, BRCA1 carriers have a 4-fold increased risk of colon cancer, whereas male carriers face a 3-fold increased risk of prostate cancer. Cells lacking BRCA1 show defects in DNA repair by homologous recombination. OMIM

    MedGen: C0678222 C0006142 C0677776 C1458155 OrphaNet: 145 227535 180250
  • Fanconi anemia, complementation group S (FANCS)

    A form of Fanconi anemia, a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.
    Disease susceptibility is associated with variations affecting the gene represented in this entry. OMIM

    MedGen: C2676676 C1140680 C0027672
  • Pancreatic cancer 4 (PNCA4)

    A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.
    Disease susceptibility is associated with variations affecting the gene represented in this entry. OMIM

    MedGen: C0027672
  • Ovarian cancer (OC)

    The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.
    Disease susceptibility is associated with variations affecting the gene represented in this entry. OMIM

    MedGen: C0919267 OrphaNet: 145
PDB and PDB position 4y2g ~> 1720 (Explore)
gnomAD Exome Allele Frequency: 0.00017531
Genome Allele Frequency: 0.0001273723
gnomAD
Pathogenicity benign according to VKGL
Literature for His201Tyr in HDAC8 Not present
Literature for similar variants in homologous proteins Not present

Literature

Literature for Thr1720Ala in BRCA1

There is no literature available for this specific variant

Literature for similar variants in homologous proteins

There is no literature available for variants in a homologous proteins

corona.ai classification

Classification: benign according to VKGL

This variant was found in the VKGL dataset. According to this authoritative source this variant is classified as benign. A prediction is available for this variant, but this source takes precedence in our classification.

corona.ai prediction details

Prediction: benign 34%

The Thr1720Ala mutation in the protein has been classified as benign by our ensemble classifier system, with baseline confidence. There is a 72% agreement between all subclassifiers.

Data quality

Data quality for this region is considered good. This means that enhanced, deep alignments are present and there is a variety of data for the algorithm to predict from.

Prediction factors

External models have estimated which sets of features contributed primarily to the classification. These sets of features are listed here.

Primary contributing factors

  • Structural features point towards benign
  • Alignment depth features point towards pathogenic
  • Protein evolutionary pressure points towards pathogenic
  • Alignment diversity points towards benign

Evolutionary pressure

Conservation

The wildtype was observed in 43.89% of the 998 sequences analyzed. The variant type was observed in 1.10% of observed sequences.


This residue is involved in 2 Hydrogen Bonds, 3 Hydrophobic interactions.

Interaction statistics were calculated using advanced molecular optimization techniques and may not be visible in the plain PDB file. Please download the YASARA scene to explore the interactions in more detail.